Meir Medical Center, Clalit Health Services and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Meir Medical Center, Clalit Health Services and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Oncologist. 2019 Dec;24(12):e1471-e1475. doi: 10.1634/theoncologist.2019-0272. Epub 2019 Jul 25.
mutations are the most frequent mutations causing homologous recombination defects in epithelial ovarian cancers (EOC). Germline mutation carriers are heterozygous for the mutation and harbor one defective allele in all cells. This has been hypothesized to cause increased susceptibility to DNA damage in healthy cells as well as neoplastic ones. Our objective was to assess chemotherapy-associated toxicities in patients with epithelial ovarian cancer with and without a germline mutation.
A retrospective cohort study of patients with EOC receiving first-line platinum-based chemotherapy at a single center between 2006 and 2016. Indices of chemotoxicity, including blood counts, transfusion requirements, granulocyte colony-stimulating factor (gCSF) prescriptions, episodes of febrile neutropenia, and treatment delays were compared for mutation carriers and noncarriers.
A total of 90 women met the inclusion criteria, including 31 mutation carriers (34%) and 59 noncarriers (66%). Mean hemoglobin, neutrophil count, and platelet counts during treatment were comparable for the two patient groups. There was a trend toward a higher frequency of hematological events in mutation carriers (neutropenia <1500 per mL: 6% vs. 0%, = .12; thrombocytopenia <100,000 per mL: 23% vs. 9%, = .07), but these differences were not statistically significant. Similarly, no significant differences were found in surrogates of bone marrow toxicity such as blood transfusions, use of gCSF, episodes of febrile neutropenia, or treatment delays.
mutation carriers and noncarriers receiving first-line platinum-based chemotherapy for EOC have similar hematologic toxicity profiles. Clinicians treating these patients can be reassured that chemotherapy dosing or schedule do not require adjustment in patients carrying mutations.
Patients with ovarian cancer carrying mutations are more likely to have serous tumors and present with higher CA125 levels. Germline mutation status is not associated with increased frequency of adverse hematologic events among patients with ovarian cancer being treated with first-line platinum-based chemotherapy. Germline mutations are also not associated with more treatment delays or a lower number of courses completed in this patient population. These findings should reassure practitioners engaged in care for patients with ovarian cancer that mutation status most likely will not affect chemotherapy dosing or schedule.
突变是导致上皮性卵巢癌（EOC）同源重组缺陷的最常见突变。种系突变携带者为该突变的杂合子，所有细胞中均携带一个有缺陷的等位基因。据推测，这会导致健康细胞和肿瘤细胞更容易受到 DNA 损伤。我们的目的是评估携带和不携带种系 突变的上皮性卵巢癌患者的化疗相关毒性。
这是一项回顾性队列研究，纳入了 2006 年至 2016 年期间在单一中心接受一线铂类化疗的 EOC 患者。比较了种系 突变携带者和非携带者的化疗毒性指数，包括血细胞计数、输血需求、粒细胞集落刺激因子（gCSF）处方、发热性中性粒细胞减少症发作和治疗延迟。
共有 90 名女性符合纳入标准，包括 31 名种系 突变携带者（34%）和 59 名非携带者（66%）。两组患者在治疗期间的平均血红蛋白、中性粒细胞计数和血小板计数相似。种系 突变携带者的血液学事件发生率较高（中性粒细胞<1500/μL：6%比 0%， =.12；血小板<100,000/μL：23%比 9%， =.07），但差异无统计学意义。同样，在骨髓毒性的替代指标（如输血、gCSF 应用、发热性中性粒细胞减少症发作或治疗延迟）方面也未发现显著差异。
接受一线铂类化疗治疗上皮性卵巢癌的种系 突变携带者和非携带者具有相似的血液学毒性特征。治疗这些患者的临床医生可以放心，携带 突变的患者不需要调整化疗剂量或方案。
携带 突变的卵巢癌患者更有可能患有浆液性肿瘤，且 CA125 水平更高。在接受一线铂类化疗的卵巢癌患者中，种系 突变状态与不良血液学事件的发生频率增加无关。在这一患者人群中，种系 突变也与治疗延迟或完成疗程数减少无关。这些发现应该使参与卵巢癌患者治疗的临床医生放心，种系 突变状态不太可能影响化疗剂量或方案。
