Witkowski Leora, Goudie Catherine, Ramos Pilar, Boshari Talia, Brunet Jean-Sebastien, Karnezis Anthony N, Longy Michel, Knost James A, Saloustros Emmanouil, McCluggage W Glenn, Stewart Colin J R, Hendricks William P D, Cunliffe Heather, Huntsman David G, Pautier Patricia, Levine Douglas A, Trent Jeffrey M, Berchuck Andrew, Hasselblatt Martin, Foulkes William D
Department of Human Genetics, McGill University, Montreal, QC, Canada.
Department of Pediatrics, McGill University, Montreal, QC, Canada.
Gynecol Oncol. 2016 Jun;141(3):454-460. doi: 10.1016/j.ygyno.2016.03.013. Epub 2016 Mar 19.
Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is an aggressive tumor, with long term survival at ~30% in early stage disease. SCCOHT is caused by germline and somatic SMARCA4 mutations, but the effect of the mutation type on patients remains unknown. Furthermore, the rarity of SCCOHT has resulted in varied treatment, with no standardized protocols. We analyzed 293 cases to determine the effect of treatment modalities and SMARCA4 mutations on patient diagnosis and outcome.
In 293 SCCOHT patients we collected information on age and stage at diagnosis, treatment modality (surgery, chemotherapy, radiotherapy, and/or high-dose chemotherapy with autologous stem cell rescue (HDC-aSCR)), SMARCA4 mutation origin (germline/somatic), and overall survival. Cox analysis and log-rank tests were performed on 257 cases with available survival data.
The strongest prognostic factors were stage at diagnosis (p=2.72e-15) and treatment modality (p=3.87e-13). For FIGO stages II-IV, 5-year survival was 71% for patients who received HDC-aSCR, compared to 25% in patients who received conventional chemotherapy alone following surgery (p=0.002). Patients aged ≥40 had a worse outcome than younger patients (p=0.04). Twenty-six of 60 tested patients carried a germline SMARCA4 mutation, including all patients diagnosed <15years; carriers presented at a younger age than non-carriers (p=0.02).
Stage at diagnosis is the most significant prognostic factor in SCCOHT and consolidation with HDC-aSCR may provide the best opportunity for long-term survival. The large fraction of SMARCA4 germline mutations carriers warrants genetic counseling for all patients.
卵巢高钙血症型小细胞癌（SCCOHT）是一种侵袭性肿瘤，早期疾病的长期生存率约为30%。SCCOHT由种系和体细胞SMARCA4突变引起，但突变类型对患者的影响尚不清楚。此外，SCCOHT的罕见性导致了治疗方法的多样化，没有标准化方案。我们分析了293例病例，以确定治疗方式和SMARCA4突变对患者诊断和预后的影响。
在293例SCCOHT患者中，我们收集了诊断时的年龄和分期、治疗方式（手术、化疗、放疗和/或自体干细胞救援的高剂量化疗（HDC-aSCR））、SMARCA4突变起源（种系/体细胞）和总生存期的信息。对257例有可用生存数据的病例进行了Cox分析和对数秩检验。
最强的预后因素是诊断时的分期（p=2.72e-15）和治疗方式（p=3.87e-13）。对于国际妇产科联盟（FIGO）II-IV期，接受HDC-aSCR的患者5年生存率为71%，而术后仅接受传统化疗的患者为25%（p=0.002）。年龄≥40岁的患者预后比年轻患者差（p=0.04）。60例接受检测的患者中有26例携带种系SMARCA4突变，包括所有诊断时年龄<15岁的患者；携带者的发病年龄比非携带者年轻（p=0.02）。
诊断时的分期是SCCOHT最重要的预后因素，采用HDC-aSCR巩固治疗可能为长期生存提供最佳机会。大部分SMARCA4种系突变携带者需要对所有患者进行遗传咨询。
