Dueckelmann A M, Fink D, Harter P, Heinzelmann V, Marth C, Mueller M, Reinthaller A, Tamussino K, Wimberger P, Sehouli J
Charité Universitätsmedizin Berlin, Berlin, Germany.
University Hospital of Zurich, Zürich, Switzerland.
Arch Gynecol Obstet. 2018 Apr;297(4):837-846. doi: 10.1007/s00404-018-4673-0. Epub 2018 Jan 22.
Ovarian, tubal, and peritoneal carcinomas primarily affect the peritoneal cavity, and they are typically diagnosed at an advanced tumor stage (Foley, Rauh-Hain, del Carmen in Oncology (Williston Park) 27:288-294, 2013). In the course of primary surgery, postoperative tumor residuals are, apart from the tumor stage, the strongest independent factors of prognosis (du Bois, Reuss, Pujade-Lauraine, Harter, Ray-Coquard, Pfisterer in Cancer 115:1234-1244, 2009). Due to improved surgical techniques, including the use of multi-visceral procedures, macroscopic tumor clearance can be achieved in oncological centers, in most cases (Harter, Muallem, Buhrmann et al in Gynecol Oncol 121:615-619, 2011). However, to date, it has not been shown that peritoneal carcinomatosis is, per se, an independent factor of prognosis or that it excludes the achievement of tumor clearance. Several studies have shown that a preceding drug therapy in peritoneal carcinomatosis could positively influence the overall prognosis (Trimbos, Trimbos, Vergote et al in J Natl Cancer Inst 95:105-112, 2003). In relapses of ovarian carcinoma, studies have shown that peritoneal carcinomatosis is a negative predictor of complete tumor resection; however, when it is possible to resect the tumor completely, peritoneal carcinomatosis does not play a role in the prognosis (Harter, Hahmann, Lueck et al in Ann Surg Oncol 16:1324-1330, 2009).
PIPAC is a highly experimental method for treating patients with ovarian, tubal, and peritoneal cancer. To date, only three studies have investigated a total of 184 patients with peritoneal carcinomatosis (Grass, Vuagniaux, Teixeira-Farinha, Lehmann, Demartines, Hubner in Br J Surg 104:669-678, 2017). Only some of those studies were phase I/II studies that included PIPAC for patients with different indications and different cancer entities. It is important to keep in mind that the PIPAC approach is associated with relatively high toxicity. To date, no systematic dose-finding studies have been reported. Moreover, no studies have reported improvements in progression-free or overall survival associated with PIPAC therapy.
Randomized phase III studies are required to evaluate the effect of this therapy compared to other standard treatments (sequential or simultaneous applications with systemic chemotherapy). In cases of ovarian, tubal, and peritoneal cancer, PIPAC should not be performed outside the framework of prospective, controlled studies.
卵巢癌、输卵管癌和腹膜癌主要累及腹膜腔，通常在肿瘤晚期被诊断出来（Foley、Rauh-Hain、del Carmen，《肿瘤学》（威利斯顿帕克）27:288 - 294，2013年）。在初次手术过程中，除肿瘤分期外，术后肿瘤残留是最强的独立预后因素（du Bois、Reuss、Pujade-Lauraine、Harter、Ray-Coquard、Pfisterer，《癌症》115:1234 - 1244，2009年）。由于手术技术的改进，包括多脏器手术的应用，在大多数肿瘤中心，多数情况下可实现宏观肿瘤清除（Harter、Muallem、Buhrmann等，《妇科肿瘤学》121:615 - 619，2011年）。然而，迄今为止，尚未表明腹膜癌病本身是一个独立的预后因素，也未表明它排除肿瘤清除的可能性。多项研究表明，在腹膜癌病之前进行药物治疗可对总体预后产生积极影响（Trimbos、Trimbos、Vergote等，《美国国家癌症研究所杂志》95:105 - 112，2003年）。在卵巢癌复发中，研究表明腹膜癌病是肿瘤完全切除的负性预测因素；然而，当能够完全切除肿瘤时，腹膜癌病对预后无影响（Harter、Hahmann、Lueck等，《外科肿瘤学年鉴》16:1324 - 1330，2009年）。
腹腔内热灌注化疗（PIPAC）是一种治疗卵巢癌、输卵管癌和腹膜癌患者的高度实验性方法。迄今为止，仅有三项研究共调查了184例腹膜癌病患者（Grass、Vuagniaux、Teixeira-Farinha、Lehmann、Demartines、Hubner，《英国外科杂志》104:669 - 678，2017年）。其中只有部分研究是I/II期研究，纳入了不同适应证和不同癌症实体的患者接受PIPAC治疗。必须牢记，PIPAC方法具有相对较高的毒性。迄今为止，尚未报告系统性的剂量探索研究。此外，也没有研究报告PIPAC治疗与无进展生存期或总生存期的改善相关。
需要进行随机III期研究，以评估这种治疗与其他标准治疗（与全身化疗序贯或同时应用）相比的效果。对于卵巢癌、输卵管癌和腹膜癌患者，不应在非前瞻性对照研究的框架之外进行PIPAC治疗。
