我们将接受过一种治疗,未使用铂类化疗的间期(无铂间期)≥6个月并且研究者确定肿瘤可切除(切除至无肉眼可见的残留病灶)的复发性卵巢癌患者随机分组,分别接受二次肿瘤细胞减灭术+后续铂类化疗或接受单独铂类化疗.
we randomly assigned patients with recurrent ovarian cancer who had received one previous therapy, had an interval during which no platinum-based chemotherapy was used (platinum-free interval) of 6 months or more, and had investigator-determined resectable disease (to no macroscopic residual disease) to undergo secondary surgical cytoreduction and then receive platinum-based chemotherapy or to receive platinum-based chemotherapy alone.
辅助化疗(紫杉醇-卡铂或吉西他滨-卡铂)和贝伐珠单抗的应用由研究者决定.
adjuvant chemotherapy (paclitaxel-carboplatin or gemcitabine-carboplatin) and use of bevacizumab were at the discretion of the investigator.
共计485例患者被随机分组,其中240例被分配接受二次肿瘤细胞减灭术+后续化疗,245例被分配接受单独化疗.
a total of 485 patients underwent randomization, 240 to secondary cytoreduction before chemotherapy and 245 to chemotherapy alone.
在被分配接受手术并实际接收了手术的患者中,67%完成了肉眼完全切除.
complete gross resection was achieved in 67 % of the patients assigned to surgery who underwent the procedure.
所有患者中有84%接受了铂类化疗+贝伐珠单抗治疗,以及后续贝伐珠单抗维持治疗,并且此类患者在两组之间均衡分布.
platinum-based chemotherapy with bevacizumab followed by bevacizumab maintenance was administered to 84 % of the patients overall and was equally distributed between the two groups.
死亡的风险比(手术vs.非手术)为1.29(95%CI,0.97~1.72;P=0.08),相当于中位总生存期分别为50.6个月和64.7个月.
the hazard ratio for death (surgery vs. no surgery) was 1.29 (95 % confidence interval [ CI ], 0.97 to 1.72; P = 0.08), which corresponded to a median overall survival of 50.6 months and 64.7 months, respectively.
针对无铂间期和化疗方案选择所做的校正未改变效应.
adjustment for platinum-free interval and chemotherapy choice did not alter the effect.
疾病进展或死亡的风险比(手术vs.非手术)为0.82(95%CI,0.66~1.01;中位无进展生存期,分别为18.9个月和16.2个月).
the hazard ratio for disease progression or death (surgery vs. no surgery) was 0.82 (95 % CI, 0.66 to 1.01; median progression-free survival, 18.9 months and 16.2 months, respectively).
30日时的手术发病率为9%;1例患者(0.4%)死于术后并发症.
surgical morbidity at 30 days was 9 %; 1 patient (0.4 %) died from postoperative complications.
患者报告术后生活质量显著降低,但康复后两组的生活质量无显著差异.
patient-reported quality of life decreased significantly after surgery but did not differ significantly between the two groups after recovery.
在纳入对铂类药物敏感的复发性卵巢癌患者的这项试验中,二次肿瘤细胞减灭术+后续化疗组的总生存期未超过单独化疗组(由美国国立癌症研究所[NationalCancerInstitute]等资助;GOG-0213在ClinicalTrials.gov注册号为NCT00565851).
in this trial involving patients with platinum-sensitive, recurrent ovarian cancer, secondary surgical cytoreduction followed by chemotherapy did not result in longer overall survival than chemotherapy alone. (Funded by the National Cancer Institute and others; GOG-0213 ClinicalTrials.gov number, NCT00565851.)
美国癌症学会(AmericanCancerSociety)估计,2019年将有约22,500名女性被诊断为上皮性卵巢癌,原发性腹膜癌或输卵管癌(统称为"卵巢"癌),将有约14,000人死于卵巢癌1.
the American Cancer Society has estimated that in 2019 approximately 22,500 women would be diagnosed with epithelial ovarian, primary peritoneal, or fallopian-tube (" ovarian ") cancer, and 14,000 would die.1
虽然并无随机试验数据证明初次肿瘤细胞减灭术可带来生存获益,但荟萃分析支持这一疗法2-4.
despite the absence of randomized data showing a survival benefit conferred by primary cytoreductive surgery, meta-analyses support the approach.2-4
理论上而言,尽最大努力手术可能有助于克服固有耐药,增加药物灌注,增强宿主免疫应答,增加肿瘤细胞的生长分数以及避免铂类辅助治疗和紫杉类药物全身性治疗后的获得性耐药5-7.
theoretically, maximal surgical effort may help overcome intrinsic drug resistance, increase drug perfusion, enhance host immunologic response, increase the growth fraction of tumor cells, and circumvent acquired drug resistance after adjuvant platinum-based and taxane-based systemic therapy.5-7
但遗憾的是,有80%患者的卵巢癌会复发.
unfortunately, recurrent disease develops in more than 80 % of women.
复发患者的10年无病生存率极低,低于15%8.
the 10-year rates of disease-free survival among patients with recurrent disease are abysmal and are below 15 %.8
考虑到初次肿瘤细胞减灭术的广泛应用,人们积极考虑将该疗法用于复发患者也就不足为奇了,尤其是适合接受铂类再诱导治疗的患者(如铂类药物治疗后的无治疗间期较长的患者)及有孤立病灶或病灶体积有限的患者.
given the widespread adoption of primary surgical cytoreduction, it is not surprising that the approach is also strongly considered for patients with recurrent disease - particularly those who are considered to be candidates for platinum reinduction (e.g., a prolonged treatment-free interval after platinum therapy) and those with isolated or limited-volume recurrent disease.
大量的单机构和多机构回顾性综述和荟萃分析增强了对该手术的支持,这些综述和分析表明,获益最大的患者是术后无或几乎无残留病灶的患者以及对铂类药物敏感的患者3,9-12.
numerous single-institution and multi-institution retrospective reviews and meta-analyses have bolstered support for the procedure, showing that patients who had the greatest benefit were those with little or no postoperative residual disease and those considered to be platinum-sensitive.3,9-12
美国国家综合癌症网络(NationalComprehensiveCancerNetwork)的现行指南将二次肿瘤细胞减灭术列为之前通过化疗达到完全缓解后,无治疗间期≥6个月患者的可选治疗方案13.
current guidelines from the National Comprehensive Cancer Network list secondary cytoreduction as a treatment option for patients with a treatment-free interval of 6 months or more after a complete remission from previous chemotherapy.13
这些证据的一个明显局限性是患者选择偏倚,不开展随机临床试验的情况下,患者选择偏倚难以控制.
a clear limitation of this body of evidence is bias in patient selection, which is not easily controlled without a randomized clinical trial.
此外,在挽救治疗有效,对铂类药物敏感的复发性卵巢癌患者中,目前已经有了用作维持治疗且无进展生存期获益得到证实的贝伐珠单抗和多腺苷二磷酸核糖聚合酶(PARP)抑制剂,在这种情况下,阐明二次肿瘤细胞减灭术在复发性卵巢癌治疗中的作用具有重要意义14-18.
furthermore, with the availability of bevacizumab and poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors as maintenance medical treatments with proven progression-free survival benefit among patients with platinum-sensitive, recurrent ovarian cancer who have a response to salvage therapy, it is important to clarify the role of secondary cytoreductive surgery in this disease.14-18
因此,我们设计了妇科肿瘤学组(GynecologicOncologyGroup,GOG)-0213试验,目的是在被认为适合手术,对铂类药物敏感的复发性卵巢癌患者中评估二次肿瘤细胞减灭术可否延长总生存期.
therefore, we designed the Gynecologic Oncology Group (GOG) -0213 trial to assess whether secondary cytoreduction would increase overall survival among women with platinum-sensitive, recurrent ovarian cancer who otherwise were considered to be surgical candidates.
GOG-0213试验是一项开放标签,3期,多中心,国际性随机临床试验,目的是评估以下两项临床相关假设:紫杉醇和卡铂化疗加用贝伐珠单抗+后续贝伐珠单抗维持治疗可改善总生存期(化疗目的),以及在对铂类药物敏感,适合手术的患者中,二次肿瘤细胞减灭术可改善总生存期(手术目的).
the GOG-0213 trial is an open-label, phase 3, multicenter, international, randomized clinical trial designed to assess two clinically relevant hypotheses: that bevacizumab added to paclitaxel and carboplatin chemotherapy followed by maintenance bevacizumab improves overall survival (chemotherapy objective) and that secondary surgical cytoreduction in platinum-sensitive, surgically amenable patients improves overall survival (surgical objective).
试验设计和患者特征已经发表,对化疗目的所做的成功评估也已经发表14.
the trial design and patient characteristics have been reported previously, as has the successful assessment of the chemotherapy objective.14