Gynecological Cancer Centre, Royal Hospital for Women, School of Women's and Children's Health, University of New South Wales, Sydney, NSW, 2031, Australia.
Gynecological Cancer Centre, Hospital for Women, University of Basel, Spitalstrasse 21, 4021, Basel, Switzerland.
J Cancer Res Clin Oncol. 2020 Mar;146(3):695-704. doi: 10.1007/s00432-019-03091-y. Epub 2020 Jan 28.
Malignant mixed Mullerian tumors of endometrial (MMMT-E) and ovarian (MMMT-O) origin are associated with poor prognosis. Suggestively epithelial-driven tumors, their treatment has shifted from anthracycline or ifosfamide-based towards taxane-based chemotherapy. It remains unclear whether this change associates with better outcomes.
A conjoined Australian and Swiss patient cohort of MMMT-E (N = 103) and MMMT-O (N = 17) was compared to patients with adenocarcinoma of the endometrium (EC, N = 172) and ovary (OC, N = 189). Clinicopathological characteristics, FIGO stage, first-line treatment, and patient outcomes were analyzed. The generated hypothesis was verified in an US-American cohort with high-grade serous ovarian cancer (HGSOC, N = 1290) and MMMT-O (N = 450) using immunohistochemistry and next-generation sequencing.
Early stage I/II MMMT-E showed a survival plateau after 2.5 years, with no recurrence or death observed afterwards. Relapse-free survival was significantly worse in MMMT-E treated with platinum/taxanes (P = 0.024) compared to non-taxane regimen. Hypothesizing that also MMMT-O might benefit from an adjuvant non-paclitaxel regimen, a second independent cohort of MMMT-O and HGSOC patients was examined. p53 mutations dominated in both cancers with comparable frequency. PI3KCA and KRAS mutations were less frequent: they were more frequent in MMMT-O than in HGSOC (P = 0.015 and P = 0.018, respectively). MMMT-O responded better to a combination of carboplatin with anthracyclines than with taxanes (73.9% vs. 39.4%).
Early stage I/II MMMT-E patients have excellent prognosis if no recurrence has appeared within the first 2.5 years. In MMMT-E, platinum/anthracycline or ifosfamide regimen associated with better outcomes than platinum/taxanes regimens. This might also apply to MMMT-O.
子宫内膜（MMMT-E）和卵巢（MMMT-O）来源的恶性混合 Müllerian 肿瘤与预后不良相关。这些肿瘤提示为上皮驱动型肿瘤，其治疗已从蒽环类或异环磷酰胺为基础的治疗转向紫杉烷类化疗。目前尚不清楚这种变化是否与更好的结果相关。
将澳大利亚和瑞士的 MMMT-E（N=103）和 MMMT-O（N=17）患者队列与子宫内膜腺癌（EC，N=172）和卵巢癌（OC，N=189）患者进行比较。分析了临床病理特征、FIGO 分期、一线治疗和患者结局。该假说在美国高级别浆液性卵巢癌（HGSOC，N=1290）和 MMMT-O（N=450）患者中通过免疫组化和下一代测序进行了验证。
早期Ⅰ/Ⅱ期 MMMT-E 在 2.5 年后出现生存平台，此后无复发或死亡。接受铂类/紫杉烷治疗的 MMMT-E 患者无复发生存率明显较差（P=0.024），而非紫杉烷方案。假设 MMMT-O 也可能受益于辅助非紫杉醇方案，因此检查了第二个独立的 MMMT-O 和 HGSOC 患者队列。在两种癌症中，p53 突变均占主导地位，且频率相当。PI3KCA 和 KRAS 突变较少：它们在 MMMT-O 中比在 HGSOC 中更常见（P=0.015 和 P=0.018）。MMMT-O 对卡铂联合蒽环类药物的反应优于紫杉醇类药物（73.9% vs. 39.4%）。
如果在最初的 2.5 年内没有出现复发，早期Ⅰ/Ⅱ期 MMMT-E 患者预后极好。在 MMMT-E 中，铂类/蒽环类或异环磷酰胺方案的治疗结果优于铂类/紫杉烷方案。这可能也适用于 MMMT-O。
