■我们比较了相对收益,术中腹膜热化疗+细胞减灭术±全身化疗与细胞减灭术±全身化疗或单纯全身化疗对结肠直肠腹膜转移患者的危害和成本效益,通过系统评价胃癌或卵巢癌,元分析和基于模型的成本效用分析。
■我们搜索了MEDLINE,EMBASE,科克伦图书馆和科学引文索引,ClinicalTrials.gov和WHOICTRP试验登记至2022年4月14日。我们仅包括解决研究目标的随机对照试验。我们使用Cochrane偏倚风险工具版本2来评估随机对照试验中的偏倚风险。在适用时,我们使用随机效应模型进行数据合成。对于成本效益分析,我们使用美国国家健康与护理卓越研究所推荐的方法进行了基于模型的成本-效用分析.
■系统评价包括总共8项随机对照试验(7项随机对照试验,955名参与者纳入定量分析)。除III期或更高的上皮性卵巢癌以外的所有比较仅包含一项试验,表明缺乏提供数据的随机对照试验。对于结直肠癌,术中腹腔热化疗+细胞减灭术+全身化疗可能导致全因死亡率几乎没有差异(60.6%vs.60.6%;风险比1.00,95%置信区间0.63至1.58),与细胞减灭术±全身化疗相比,可能会增加严重不良事件的比例(25.6%vs.15.2%;风险比1.69,95%置信区间1.03~2.77)。与单纯以氟尿嘧啶为基础的全身化疗相比,术中腹腔热化疗+细胞减灭术+全身化疗可能会降低全因死亡率(40.8%vs.60.8%;风险比0.55,95%置信区间0.32至0.95)。对于胃癌,术中腹腔热化疗+细胞减灭术+全身化疗与细胞减灭术+全身化疗或单纯全身化疗对全因死亡率的影响存在高度不确定性.对于接受间隔细胞减灭术的III期或更高的上皮性卵巢癌,与细胞减灭术+全身化疗相比,术中腹腔热化疗+细胞减灭术+全身化疗可能降低全因死亡率(46.3%vs.57.4%;风险比0.73,95%置信区间0.57~0.93)。术中腹腔热化疗+细胞减灭术+全身化疗可能与细胞减灭术+全身化疗治疗结直肠癌的成本效益不同,但对于其余的比较可能是成本效益。
■我们无法按计划获取个体参与者数据。每次比较的随机对照试验数量有限,以及与健康相关的生活质量数据匮乏,这意味着随着新证据(来自偏倚风险较低的试验)的出现,建议可能会发生变化。
■在患有结肠直肠癌腹膜转移的人中,腹膜转移有限,并且可能承受大手术,在常规临床实践中不宜使用术中腹腔热化疗+细胞减灭术+全身化疗(强烈推荐)。对于胃癌和腹膜转移患者,是否应提供术中高温腹膜化疗+细胞减灭术+全身化疗或细胞减灭术+全身化疗存在相当大的不确定性(无推荐)。术中腹腔热化疗+细胞减灭术+全身化疗应常规用于III期或更高级别上皮性卵巢癌和局限于腹部的转移患者,需要并可能在化疗后经受间期细胞减灭术(强烈推荐)。
■需要更多的随机对照试验。
■本研究注册为PROSPEROCRD42019130504。
■该奖项由美国国家卫生与护理研究所(NIHR)卫生技术评估计划(NIHR奖编号:17/135/02)资助,并在《卫生技术评估》中全文发布。28号51.有关更多奖项信息,请参阅NIHR资助和奖励网站。
肠癌,卵巢或胃可以扩散到腹部(“腹膜转移”)。通过注射或片剂(“全身化疗”)给予的化疗(使用旨在杀死癌细胞的药物)是主要的治疗选择之一。对于增加细胞减灭术(细胞减灭术;切除癌症的手术)和“术中腹膜热化疗”(在细胞减灭术中进入腹部衬里的热化疗)是否有益,存在不确定性。我们回顾了截至2022年4月14日发表的所有医学文献信息,以回答上述不确定性。我们从八项试验中发现了以下内容,包括约1000名参与者。在患有肠癌腹膜转移的人中,与细胞减灭术+全身化疗相比,术中腹腔热化疗+细胞减灭术+全身化疗可能不会带来任何益处,也会增加伤害。与单纯全身化疗相比,细胞减灭术+全身化疗似乎能提高生存率。对于胃癌腹膜转移患者的最佳治疗方法存在不确定性。在患有卵巢癌腹膜转移的女性中,在进行细胞减灭术之前需要进行全身化疗以缩小癌症以进行手术(“晚期卵巢癌”),与细胞减灭术+全身化疗相比,术中腹腔热化疗+细胞减灭术+全身化疗可能会增加生存率。在能够承受大手术并且可以切除癌症的人中,肿瘤细胞减灭术+全身化疗应提供给患有肠癌腹膜转移的人,对于“晚期卵巢癌”腹膜转移的女性,应提供术中高温腹膜化疗+细胞减灭术+全身化疗。胃癌治疗的不确定性仍在继续。该奖项由美国国家卫生与护理研究所(NIHR)卫生技术评估计划(NIHR奖ref:17/135/02)资助,并在《卫生技术评估》中全文发表;28号51.有关更多奖项信息,请参阅NIHR资助和奖励网站。
UNASSIGNED: We compared the relative benefits, harms and cost-effectiveness of hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery ± systemic chemotherapy versus cytoreductive surgery ± systemic chemotherapy or systemic chemotherapy alone in people with peritoneal metastases from colorectal, gastric or ovarian cancers by a systematic
review, meta-analysis and model-based cost-utility analysis.
UNASSIGNED: We searched MEDLINE, EMBASE, Cochrane Library and the Science Citation Index, ClinicalTrials.gov and WHO ICTRP trial registers until 14 April 2022. We included only randomised controlled trials addressing the research objectives. We used the Cochrane risk of bias tool version 2 to assess the risk of bias in randomised controlled trials. We used the random-effects model for data synthesis when applicable. For the cost-effectiveness analysis, we performed a model-based cost-utility analysis using methods recommended by The National Institute for Health and Care Excellence.
UNASSIGNED: The systematic
review included a total of eight randomised controlled trials (seven randomised controlled trials, 955 participants included in the quantitative analysis). All comparisons other than those for stage III or greater epithelial ovarian cancer contained only one trial, indicating the paucity of randomised controlled trials that provided data. For colorectal cancer, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably results in little to no difference in all-cause mortality (60.6% vs. 60.6%; hazard ratio 1.00, 95% confidence interval 0.63 to 1.58) and may increase the serious adverse event proportions compared to cytoreductive surgery ± systemic chemotherapy (25.6% vs. 15.2%; risk ratio 1.69, 95% confidence interval 1.03 to 2.77). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably decreases all-cause mortality compared to fluorouracil-based systemic chemotherapy alone (40.8% vs. 60.8%; hazard ratio 0.55, 95% confidence interval 0.32 to 0.95). For gastric cancer, there is high uncertainty about the effects of hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy versus cytoreductive surgery + systemic chemotherapy or systemic chemotherapy alone on all-cause mortality. For stage III or greater epithelial ovarian cancer undergoing interval cytoreductive surgery, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably decreases all-cause mortality compared to cytoreductive surgery + systemic chemotherapy (46.3% vs. 57.4%; hazard ratio 0.73, 95% confidence interval 0.57 to 0.93). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy may not be cost-effective versus cytoreductive surgery + systemic chemotherapy for colorectal cancer but may be cost-effective for the remaining comparisons.
UNASSIGNED: We were unable to obtain individual participant data as planned. The limited number of randomised controlled trials for each comparison and the paucity of data on health-related quality of life mean that the recommendations may change as new evidence (from trials with a low risk of bias) emerges.
UNASSIGNED: In people with peritoneal metastases from colorectal cancer with limited peritoneal metastases and who are likely to withstand major surgery, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy should not be used in routine clinical practice (strong recommendation). There is considerable uncertainty as to whether hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy or cytoreductive surgery + systemic chemotherapy should be offered to patients with gastric cancer and peritoneal metastases (no recommendation). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy should be offered routinely to women with stage III or greater epithelial ovarian cancer and metastases confined to the abdomen requiring and likely to withstand interval cytoreductive surgery after chemotherapy (strong recommendation).
UNASSIGNED: More randomised controlled trials are necessary.
UNASSIGNED: This study is registered as PROSPERO CRD42019130504.
UNASSIGNED: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/135/02) and is published in full in Health Technology Assessment; Vol. 28, No. 51. See the NIHR Funding and Awards website for further award information.
Cancers of the bowel, ovary or stomach can spread to the lining of the abdomen (‘peritoneal metastases’). Chemotherapy (the use of drugs that aim to kill cancer cells) given by injection or tablets (‘systemic chemotherapy’) is one of the main treatment options. There is uncertainty about whether adding cytoreductive surgery (cytoreductive surgery; an operation to remove the cancer) and ‘hyperthermic intraoperative peritoneal chemotherapy’ (warm chemotherapy delivered into the lining of the abdomen during cytoreductive surgery) are beneficial. We reviewed all the information from medical literature published until 14 April 2022, to answer the above uncertainty. We found the following from eight trials, including about 1000 participants. In people with peritoneal metastases from bowel cancer, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably does not provide any benefits and increases harm compared to cytoreductive surgery + systemic chemotherapy, while cytoreductive surgery + systemic chemotherapy appears to increase survival compared to systemic chemotherapy alone. There is uncertainty about the best treatment for people with peritoneal metastases from stomach cancer. In women with peritoneal metastases from ovarian cancer who require systemic chemotherapy before cytoreductive surgery to shrink the cancer to allow surgery (‘advanced ovarian cancer’), hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably increases survival compared to cytoreductive surgery + systemic chemotherapy. In people who can withstand a major operation and in whom cancer can be removed, cytoreductive surgery + systemic chemotherapy should be offered to people with peritoneal metastases from bowel cancer, while hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy should be offered to women with peritoneal metastases from ‘advanced ovarian cancer’. Uncertainty in treatment continues for gastric cancer. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/135/02) and is published in full in Health Technology Assessment; Vol. 28, No. 51. See the NIHR Funding and Awards website for further award information.