目标:在受横纹肌样瘤(RT)影响的儿童中,有临床,治疗性的,
结论:我们检测到女性优势显著升高,诊断时的中位年龄较低,与其他RT儿童相比,在ART(RT_ART)后受孕的RT儿童。
背景:轶事证据表明ART与RT相关。
方法:这是一项多机构回顾性调查。在我们的EU-RHAB数据库中(2010年1月至2018年1月之间诊断出的n=11/311儿童)和来自9个不同国家的EU-RHAB数据库之外(n=3)确定了通过ART构思的RT儿童。在同一时间段内,一个具有代表性的德国EU-RHAB对照队列(n=211)(EU-RHAB对照队列)被用作临床对照队列,治疗性的,和生存分析。RT_ART患儿的中位随访时间为11.5个月(0-120个月),EU-RHAB对照组为18.5个月(0-153个月)。
方法:我们分析了2010年1月至2018年1月诊断为RT_ART的14例儿童。我们使用FISH检查了肿瘤和匹配的血液样本的SMARCB1突变和拷贝数改变,多重连接依赖性探针扩增,和DNA测序。使用DNA甲基化阵列对肿瘤和/或血液样本进行DNA甲基化分析,并与相似年龄的相应对照组进行比较(n=53例接受RT的儿童肿瘤,n=38个没有胎龄小的肿瘤的儿童的血液样本)。
结果:14例RT_ART患者的诊断中位年龄为9个月(0-66个月),在EU-RHAB对照队列(16个月(范围0-253)中,明显低于RT患者的中位年龄(n=211),P=0.03)。在RT_ART队列中观察到明显的女性优势(在EU-RHAB对照队列中,M:F比:2:12对116:95,P=0.004)。14例RT_ART患者中有8例诊断为非典型畸胎瘤样横纹肌样瘤,三个是颅外的,肾外恶性横纹肌样瘤,一个患有肾脏横纹肌样肿瘤,两个患有同步肿瘤。在EU-RHAB对照队列中,原发肿瘤的位置没有显着差异(P=0.27)。14例RT_ART患者中有6例在诊断时出现转移。转移阶段与EU-RHAB对照组中的转移阶段没有显着差异(6/14vs88/211,P=1)。致病性种系变异的发生率是12例接受测试的RT_ART患者中的5例,因此,与EU-RHAB对照组没有显着差异(5/12对36/183进行了测试,P=0.35)。RT_ART患者的5年总生存率(OS)和无事件生存率(EFS)分别为42.9±13.2%和21.4±11%,分别,因此与EU-RHAB对照组(OS41.1±3.5%和EFS32.1±3.3)相当。我们没有找到其他临床医生,治疗性的,将接受RT_ART的患者与未接受ART的接受RT的儿童区别开来的结局因素(EU-RHAB对照队列)。10种肿瘤的DNA甲基化分析(非典型畸胎样RT=6,颅外,肾外恶性RT=4)和来自RT_ART患者的六个血液样本既没有显示一般DNA甲基化差异的证据,也没有潜在的印迹缺陷,分别,与对照组相比(n=53例未接受ART的患者的RT样本,P=0.51,n=38个出生小于胎龄的患者的血液样本,P=0.1205)。
结论:RT是非常罕见的恶性肿瘤,我们的结果是基于少数RT_ART患儿。
结论:这一组RT_ART患者表现出明显的女性优势,即使是RTs,诊断时的中位年龄也相当低。其他临床,治疗,结果,和分子因素与未接受ART(EU-RHAB对照队列)或其他系列报道的分子因素没有差异,也没有印痕缺陷的证据.即使在有致病性种系变异的情况下,长期生存也是可以实现的。诊断时的转移性疾病,或复发。RT_ART患者中的女性优势尚不清楚,需要进行评估,理想情况下,在较大的国际系列。
背景:M.C.F.由\'DeutscheKinderkrebsstiftung\'DKS2020.10,\''DeutscheForschungsgemeinschaft\'DFGFR1516/4-1和DeutscheKrebshilfe70113981支持。R.S.获得了DeutscheKrebshilfe70114040的赠款支持,以及KinderKrebsInitiativeBuchholz/Holm-Seppensen的基础设施支持。P.D.J.得到Else-Kroener-FreseniusStiftung的支持,并获得了DeutscheKrebshilfe的Max-Eder奖学金。M.H.由DFG(HA3060/8-1)和IZKF明斯特(Ha3/017/20)支持。BB由“德意志Kinderkrebsstiftung”DKS2020.05支持。我们宣布没有相互竞争的利益。
背景:不适用。
OBJECTIVE: In children affected by rhabdoid tumors (RT), are there clinical, therapeutic, and/or (epi-)genetic differences between those conceived following ART compared to those conceived without ART?
CONCLUSIONS: We detected a significantly elevated female predominance, and a lower median age at diagnosis, of children with RT conceived following ART (RT_ART) as compared to other children with RT.
BACKGROUND: Anecdotal evidence suggests an association of ART with RT.
METHODS: This was a multi-institutional retrospective survey. Children with RT conceived by ART were identified in our EU-RHAB database (n = 11/311 children diagnosed between January 2010 and January 2018) and outside the EU-RHAB database (n = 3) from nine different countries. A population-representative German EU-RHAB control cohort of children with RTs conceived without ART (n = 211) (EU-RHAB control cohort) during the same time period was used as a control cohort for clinical, therapeutic, and survival analyses. The median follow-up time was 11.5 months (range 0-120 months) for children with RT_ART and 18.5 months (range 0-153 months) for the EU-RHAB control cohort.
METHODS: We analyzed 14 children with RT_ART diagnosed from January 2010 to January 2018. We examined tumors and matching blood samples for SMARCB1 mutations and copy number alterations using FISH, multiplex ligation-dependent probe amplification, and DNA sequencing. DNA methylation profiling of tumor and/or blood samples was performed using DNA methylation arrays and compared to respective control cohorts of similar age (n = 53 tumors of children with RT conceived without ART, and n = 38 blood samples of children with no tumor born small for gestational age).
RESULTS: The median age at diagnosis of 14 individuals with RT_ART was 9 months (range 0-66 months), significantly lower than the median age of patients with RT (n = 211) in the EU-RHAB control cohort (16 months (range 0-253), P = 0.03). A significant female predominance was observed in the RT_ART cohort (M:F ratio: 2:12 versus 116:95 in EU-RHAB control cohort, P = 0.004). Eight of 14 RT_ART patients were diagnosed with atypical teratoid rhabdoid tumor, three with extracranial, extrarenal malignant rhabdoid tumor, one with rhabdoid tumor of the kidney and two with synchronous tumors. The location of primary tumors did not differ significantly in the EU-RHAB control cohort (P = 0.27). Six of 14 RT_ART patients presented with metastases at diagnosis. Metastatic stage was not significantly different from that within the EU-RHAB control cohort (6/14 vs 88/211, P = 1). The incidence of pathogenic germline variants was five of the 12 tested RT_ART patients and, thus, not significantly different from the EU-RHAB control cohort (5/12 versus 36/183 tested, P = 0.35). The 5-year overall survival (OS) and event free survival (EFS) rates of RT_ART patients were 42.9 ± 13.2% and 21.4 ± 11%, respectively, and thus comparable to the EU-RHAB control cohort (OS 41.1 ± 3.5% and EFS 32.1 ± 3.3). We did not find other clinical, therapeutic, outcome factors distinguishing patients with RT_ART from children with RTs conceived without ART (EU-RHAB control cohort). DNA methylation analyses of 10 tumors (atypical teratoid RT = 6, extracranial, extrarenal malignant RT = 4) and six blood samples from RT_ART patients showed neither evidence of a general DNA methylation difference nor underlying imprinting defects, respectively, when compared to a control group (n = 53 RT samples of patients without ART, P = 0.51, n = 38 blood samples of patients born small for gestational age, P = 0.1205).
CONCLUSIONS: RTs are very rare malignancies and our results are based on a small number of children with RT_ART.
CONCLUSIONS: This cohort of patients with RT_ART demonstrated a marked female predominance, and a rather low median age at diagnosis even for RTs. Other clinical, treatment, outcome, and molecular factors did not differ from those conceived without ART (EU-RHAB control cohort) or reported in other series, and there was no evidence for imprinting defects. Long-term survival is achievable even in cases with pathogenic germline variants, metastatic disease at diagnosis, or relapse. The female preponderance among RT_ART patients is not yet understood and needs to be evaluated, ideally in larger international series.
BACKGROUND: M.C.F. is supported by the \'Deutsche Kinderkrebsstiftung\' DKS 2020.10, by the \'Deutsche Forschungsgemeinschaft\' DFG FR 1516/4-1 and by the Deutsche Krebshilfe 70113981. R.S. received grant support by Deutsche Krebshilfe 70114040 and for infrastructure by the KinderKrebsInitiative Buchholz/Holm-Seppensen. P.D.J. is supported by the Else-Kroener-Fresenius Stiftung and receives a Max-Eder scholarship from the Deutsche Krebshilfe. M.H. is supported by DFG (HA 3060/8-1) and IZKF Münster (Ha3/017/20). BB is supported by the \'Deutsche Kinderkrebsstiftung\' DKS 2020.05. We declare no competing interests.
BACKGROUND: N/A.