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Abstract：
OBJECTIVE: We aimed to describe the behavior among Chinese ovarian cancer patients with RAD51D germline mutations at our institution.
METHODS: Next-generation sequencing (NGS) was conducted for the entire coding regions and exon/intron boundaries of the RAD51D genes in 781 Chinese ovarian cancer patients treated at our institution from January 1, 2015 to August 1, 2021. Clinicopathological characteristics, treatment modalities, and outcomes were assessed for ovarian cancer patients with RAD51D germline mutations.
RESULTS: RAD51D germline pathogenic mutations were detected in 1.7% (13/781) of patients in this cohort. RAD51D c. 270_271dup (p. Lys91fs) mutation was the most common mutation which was found in 7 patients (7/13, 53.1%). Patients median age at diagnosis was 58 years (range: 45-69 years). 46.2% (6/13) of them were diagnosed after 60 years. Only 1 patient (1/13, 7.7%) had a family history of ovarian or breast cancer. And 1 patient (1/13, 7.7%) had a personal history of breast cancer. The FIGO 2014 distribution by stage was: stage II in 1 patient (7.7%), stage III in 9 patients (69.2%) and stage IV in 3 patient (23.1%). 92.3% (12/13) patients had high-grade serous carcinoma. 2 patients (2/13, 15.4%) had a primary peritoneal cancer. The majority of patients in the entire cohort were reported to be platinum sensitive (92.3%, 12/13) with a platinum-free interval (PFI) of > 6 months. For patients who received PARPis for 2nd line maintenance treatment (n = 5), 2 patients discontinued PARPis treatment after 33.5 and 8.1 months of duration. Other 3 patients are still on therapy with a duration of 2.4, 13.8 and 30.1 months at the date of data cutoff. 1 patient received PARPi as salvage treatment with a duration of only 1.2 months. Nine patients (9/13, 69.2%) relapsed during follow up and all of them relapsed within 2 years after diagnosis, among which 88.9% (8/9) were classified as platinum-sensitive recurrence (PSR), and only 1 patient was classified as platinum-resistant recurrence (PRR). Median PFS for the entire cohort was 17.3 months. Median PFS for the PSR subgroup was 15.9 months. 2 patients died during follow-up. The OS of these 2 patients was 17.2 and 39.6 months. The 5-year OS rate was 67.5%.
CONCLUSIONS: RAD51D germline mutations are more frequent in Chinese ovarian cancer patients than other population. Few patients have a family history of ovarian or breast cancer, and personal history of breast cancer. Most patients are diagnosed after 50 years. The sensitivity to PARP inhibitors of patients with RAD51D germline mutations need a further analysis.
METHODS: Next-generation sequencing (NGS) was conducted for the entire coding regions and exon/intron boundaries of the RAD51D genes in 781 Chinese ovarian cancer patients treated at our institution from January 1, 2015 to August 1, 2021. Clinicopathological characteristics, treatment modalities, and outcomes were assessed for ovarian cancer patients with RAD51D germline mutations.
RESULTS: RAD51D germline pathogenic mutations were detected in 1.7% (13/781) of patients in this cohort. RAD51D c. 270_271dup (p. Lys91fs) mutation was the most common mutation which was found in 7 patients (7/13, 53.1%). Patients median age at diagnosis was 58 years (range: 45-69 years). 46.2% (6/13) of them were diagnosed after 60 years. Only 1 patient (1/13, 7.7%) had a family history of ovarian or breast cancer. And 1 patient (1/13, 7.7%) had a personal history of breast cancer. The FIGO 2014 distribution by stage was: stage II in 1 patient (7.7%), stage III in 9 patients (69.2%) and stage IV in 3 patient (23.1%). 92.3% (12/13) patients had high-grade serous carcinoma. 2 patients (2/13, 15.4%) had a primary peritoneal cancer. The majority of patients in the entire cohort were reported to be platinum sensitive (92.3%, 12/13) with a platinum-free interval (PFI) of > 6 months. For patients who received PARPis for 2nd line maintenance treatment (n = 5), 2 patients discontinued PARPis treatment after 33.5 and 8.1 months of duration. Other 3 patients are still on therapy with a duration of 2.4, 13.8 and 30.1 months at the date of data cutoff. 1 patient received PARPi as salvage treatment with a duration of only 1.2 months. Nine patients (9/13, 69.2%) relapsed during follow up and all of them relapsed within 2 years after diagnosis, among which 88.9% (8/9) were classified as platinum-sensitive recurrence (PSR), and only 1 patient was classified as platinum-resistant recurrence (PRR). Median PFS for the entire cohort was 17.3 months. Median PFS for the PSR subgroup was 15.9 months. 2 patients died during follow-up. The OS of these 2 patients was 17.2 and 39.6 months. The 5-year OS rate was 67.5%.
CONCLUSIONS: RAD51D germline mutations are more frequent in Chinese ovarian cancer patients than other population. Few patients have a family history of ovarian or breast cancer, and personal history of breast cancer. Most patients are diagnosed after 50 years. The sensitivity to PARP inhibitors of patients with RAD51D germline mutations need a further analysis.
摘要：
目的：我们旨在描述中国卵巢癌患者RAD51D种系突变的行为。
方法：对2015年1月1日至2021年8月1日在我院接受治疗的781名中国卵巢癌患者的RAD51D基因的整个编码区和外显子/内含子边界进行了下一代测序（NGS）。临床病理特征,治疗方式，并评估了具有RAD51D种系突变的卵巢癌患者的结局.
结果：在该队列中1.7%（13/781）的患者中检测到RAD51D种系致病突变。RAD51Dc。270_271dup（p。Lys91fs）突变是最常见的突变，在7例患者中发现（7/13，53.1％）。患者诊断时的中位年龄为58岁（范围：45-69岁）。其中46.2％（6/13）是在60年后诊断的。只有1例患者（1/13，7.7％）有卵巢癌或乳腺癌家族史。1例患者（1/13，7.7％）有乳腺癌病史。2014年FIGO分期分布为：1例患者的II期（7.7%），9例患者为III期（69.2％），3例患者为IV期（23.1％）。92.3%(12/13)患者为高级别浆液性癌。2例患者（2/13，15.4%）为原发性腹膜癌。据报道，整个队列中的大多数患者对铂类敏感(92.3%，12/13），无铂间隔（PFI）>6个月。对于接受PARPis进行二线维持治疗的患者（n=5），2例患者在33.5和8.1个月后停止PARPis治疗。在数据截止日期，其他3名患者仍在接受治疗，持续时间为2.4、13.8和30.1个月。1例患者接受PARPi作为抢救治疗，持续时间仅为1.2个月。随访期间复发9例(9/13,69.2%),确诊后2年内复发,其中88.9%(8/9)被归类为铂敏感复发(PSR),只有1例患者被归类为铂类耐药复发(PRR).整个队列的平均PFS为17.3个月。PSR亚组的平均PFS为15.9个月。随访期间死亡2例。2例患者的OS分别为17.2个月和39.6个月。5年OS率为67.5%。
结论：RAD51D种系突变在中国卵巢癌患者中的发生率高于其他人群。很少有患者有卵巢癌或乳腺癌家族史，和个人乳腺癌病史。大多数患者在50年后确诊。RAD51D种系突变患者对PARP抑制剂的敏感性需要进一步分析。
方法：对2015年1月1日至2021年8月1日在我院接受治疗的781名中国卵巢癌患者的RAD51D基因的整个编码区和外显子/内含子边界进行了下一代测序（NGS）。临床病理特征,治疗方式，并评估了具有RAD51D种系突变的卵巢癌患者的结局.
结果：在该队列中1.7%（13/781）的患者中检测到RAD51D种系致病突变。RAD51Dc。270_271dup（p。Lys91fs）突变是最常见的突变，在7例患者中发现（7/13，53.1％）。患者诊断时的中位年龄为58岁（范围：45-69岁）。其中46.2％（6/13）是在60年后诊断的。只有1例患者（1/13，7.7％）有卵巢癌或乳腺癌家族史。1例患者（1/13，7.7％）有乳腺癌病史。2014年FIGO分期分布为：1例患者的II期（7.7%），9例患者为III期（69.2％），3例患者为IV期（23.1％）。92.3%(12/13)患者为高级别浆液性癌。2例患者（2/13，15.4%）为原发性腹膜癌。据报道，整个队列中的大多数患者对铂类敏感(92.3%，12/13），无铂间隔（PFI）>6个月。对于接受PARPis进行二线维持治疗的患者（n=5），2例患者在33.5和8.1个月后停止PARPis治疗。在数据截止日期，其他3名患者仍在接受治疗，持续时间为2.4、13.8和30.1个月。1例患者接受PARPi作为抢救治疗，持续时间仅为1.2个月。随访期间复发9例(9/13,69.2%),确诊后2年内复发,其中88.9%(8/9)被归类为铂敏感复发(PSR),只有1例患者被归类为铂类耐药复发(PRR).整个队列的平均PFS为17.3个月。PSR亚组的平均PFS为15.9个月。随访期间死亡2例。2例患者的OS分别为17.2个月和39.6个月。5年OS率为67.5%。
结论：RAD51D种系突变在中国卵巢癌患者中的发生率高于其他人群。很少有患者有卵巢癌或乳腺癌家族史，和个人乳腺癌病史。大多数患者在50年后确诊。RAD51D种系突变患者对PARP抑制剂的敏感性需要进一步分析。
