Hyperthermic intraperitoneal chemotherapy

腹腔热化疗
  • 文章类型: Journal Article
    目的:胰腺癌腹膜转移的预后具有挑战性,有限的有效治疗选择。本研究旨在评估细胞减灭术(CRS)与腹腔热化疗(HIPEC)联合作为该患者组治疗策略的有效性和安全性。
    方法:回顾性分析2017年3月至2023年12月在北京世纪坛医院接受CRS+HIPEC治疗的胰腺癌腹膜转移患者的临床资料。这项研究的重点是评估临床特征,严重不良事件(SAE)的发生率,总生存率(OS)。
    结果:本研究共纳入10例患者。中位OS为24.2个月,表明对传统疗法的改进。虽然注意到SAE,包括2例需要额外手术干预的严重并发症,没有围手术期死亡记录.CC0/1患者的总生存时间与CC2/3患者的总生存时间没有显着差异,并且没有确定预后预测因子。
    结论:CRS和HIPEC的组合似乎是胰腺癌腹膜转移患者的可行和有希望的治疗方式,提供提高的生存率和可控的安全问题。需要进一步的研究来完善患者选择标准,并探索这种方法的长期益处。
    OBJECTIVE: Pancreatic cancer with peritoneal metastasis presents a challenging prognosis, with limited effective treatment options available. This study aims to evaluate the efficacy and safety of combining cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) as a treatment strategy for this patient group.
    METHODS: A retrospective analysis was conducted on patients with peritoneal metastasis of pancreatic cancer who underwent CRS + HIPEC treatment at Beijing Shijitan Hospital from March 2017 to December 2023. The study focused on assessing clinical features, the incidence of sever adverse events (SAEs), and overall survival (OS).
    RESULTS: A total of 10 patients were enrolled in this study. The median OS was 24.2 months, suggesting an improvement over traditional therapies. While SAEs were noted, including two cases of severe complications necessitating additional surgical interventions, no perioperative fatalities were recorded. The overall survival time for patients with CC0/1 was not significantly different from that of patients with CC2/3, and no prognostic predictors were identified.
    CONCLUSIONS: The combination of CRS and HIPEC appears to be a viable and promising treatment modality for patients with peritoneal metastasis of pancreatic cancer, offering an improved survival rate with manageable safety concerns. Further research is needed to refine patient selection criteria and to explore the long-term benefits of this approach.
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  • 文章类型: Journal Article
    围手术期白蛋白外渗伴随腹部大手术的临床后果仍未充分研究。我们回顾性分析了接受细胞减灭术(CRS)和术中腹腔热化疗(HIPEC)的患者的数据。白蛋白动力学参数,包括血清白蛋白浓度降低(ΔAlb)和白蛋白外渗水平(Albshift),从手术到术后第3天(POD)进行评估。Logistic回归分析确定了与主要并发症相关的因素。使用受试者工作特征(ROC)曲线分析评估白蛋白动力学与主要并发症的关系。手术期间血清白蛋白水平降低,随后升高。在121名被分析的患者中,25(21%)发生了主要并发症。发生重大并发症的患者在手术期间和POD3上的ΔAlb和Albshift高于未发生严重并发症的患者(12±12vs.6±14,p=0.032,和127.5(71.9)48.5(44.9),p分别<0.001)。围手术期ΔAlb和Albshift与主要并发症有关。术后3天Albshift和POD3上Albshift的ROC曲线下面积分别为0.843和0.910。术后3天的Albshift和POD3的Albshift与并发症相关(p<0.05)。总之,在接受CRS和HIPEC的患者中,围手术期白蛋白丢失与主要并发症相关.Albshift与严重并发症有关。
    The clinical consequences of perioperative albumin extravasation accompanying major abdominal surgery remain underexplored. We retrospectively reviewed the data of patients who underwent cytoreductive surgery (CRS) and hyperthermic intraoperative peritoneal chemotherapy (HIPEC). Parameters of albumin kinetics, including serum albumin concentration decrease (∆Alb) and extravasated albumin level (Albshift), were assessed from surgery until postoperative day (POD) 3. Logistic regression analysis identified factors associated with major complications. The association of albumin kinetics with major complications was evaluated using receiver operating characteristic (ROC) curve analysis. Serum albumin levels decreased during surgery and subsequently increased. Of the 121 analyzed patients, 25 (21%) developed major complications. The ∆Alb and Albshift during surgery and on POD 3 were greater in patients who developed major complications than in those who did not (12 ± 12 vs. 6 ± 14, p = 0.032, and 127.5 (71.9) vs. 48.5 (44.9), p < 0.001, respectively). Perioperative ∆Alb and Albshift were associated with major complications. The areas under the ROC curve of Albshift during the 3 days post-surgery and Albshift on POD 3 were 0.843 and 0.910, respectively. Albshift during the 3 days post-surgery and Albshift on POD 3 were correlated with complications (p < 0.05). In conclusion, perioperative albumin loss was associated with major complications in patients undergoing CRS and HIPEC. Albshift was associated with serious complications.
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  • 文章类型: Journal Article
    控制营养状况(CONUT)评分是一种新的营养指数,它整合了血清白蛋白水平,外周血淋巴细胞计数,和总胆固醇水平。这项回顾性研究探讨了其在接受细胞减灭术联合腹腔热化疗(CRS-HIPEC)的患者中的预后意义。我们纳入了436例接受CRS-HIPEC的患者,分为低(0-3)和高(4-12)CONUT得分组,并进行logistic回归分析以预测1年死亡率和术后发病率。我们的研究结果表明,高CONUT得分与一年死亡率增加相关(47.1%与20.3%,p<0.001)和发病率(39.2%vs.18.2%,p<0.001)与低CONUT评分相比。多变量回归分析证实高CONUT评分是一年死亡率(比值比:2.253,95%CI:1.014-5.005,p=0.046)和术后发病率(比值比:2.201,95%CI:1.066-4.547,p=0.033)的独立预测因子。这些结果强调了CONUT评分作为评估与CRS-HIPEC相关风险的独立指标的有效性,强调其改善风险分层的潜力。
    The Controlling Nutritional Status (CONUT) score is a novel nutritional index that integrates the serum albumin level, peripheral blood lymphocyte count, and total cholesterol level. This retrospective study explores its prognostic significance in patients undergoing cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). We included 436 patients who underwent CRS-HIPEC, categorized into low (0-3) and high (4-12) CONUT score groups, and performed logistic regression analysis to predict one-year mortality and postoperative morbidity. Our findings revealed that high CONUT scores correlate with increased one-year mortality (47.1% vs. 20.3%, p < 0.001) and morbidity (39.2% vs. 18.2%, p < 0.001) compared to low CONUT scores. Multivariable regression analysis confirmed high CONUT scores as independent predictors of one-year mortality (odds ratio: 2.253, 95% CI: 1.014-5.005, p = 0.046) and postoperative morbidity (odds ratio: 2.201, 95% CI: 1.066-4.547, p = 0.033). These results underscore the CONUT score\'s effectiveness as an independent marker for evaluating risks associated with CRS-HIPEC, emphasizing its potential to improve risk stratification.
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  • 文章类型: Journal Article
    腹膜肉瘤病是一种罕见的恶性疾病,预后差,继发于腹盆腔软组织肉瘤的腹膜播散。它的稀有性,连同特征性的组织学异质性和历史上对全身治疗的不良反应,阻止了建立具有治愈意图的广泛接受的治疗标准。在这个意义上,根治性细胞减灭术(CRS)与周围切除术和腹腔热化疗(HIPEC),广泛用于腹膜癌,效果极佳,在腹膜肉瘤病患者中没有相同的进化发展。一个由肉瘤和腹膜肿瘤外科专家组成的多学科工作组根据当前的科学证据为腹膜肉瘤病的管理制定了一系列建议,考虑到腹盆腔肉瘤的不同组织学亚组,可根据其起源引起:腹膜后肉瘤,子宫肉瘤,GIST(胃肠道间质瘤)和非GIST起源的内脏/腹膜肉瘤。本文显示了肉瘤专家对在伊比利亚-美洲关于腹膜肉瘤病管理的共识中提出的建议进行投票的结果,这是在最近举行的第三届西班牙裔-葡萄牙肉瘤治疗更新会议的庆祝活动中举行的。
    Peritoneal sarcomatosis is a rare malignant disease with a poor prognosis, secondary to peritoneal dissemination of abdominopelvic soft tissue sarcomas. Its rarity, together with the characteristic histological heterogeneity and the historically poor response to systemic treatments, has prevented the establishment of widely accepted treatment criteria with curative intent. In this sense, radical cytoreductive surgery (CRS) with peritonectomy procedures and hyperthermic intraperitoneal chemotherapy (HIPEC), widely used in peritoneal carcinomatosis with excellent results, have not had the same evolutionary development in patients with peritoneal sarcomatosis. A multidisciplinary working group of experts in sarcomas and peritoneal oncological surgery established a series of recommendations based on current scientific evidence for the management of peritoneal sarcomatosis, taking into account the different histological subgroups of abdominopelvic sarcomas that can cause it depending on their origin: retroperitoneal sarcomas, uterine sarcomas, and visceral/peritoneal sarcomas of GIST (gastrointestinal stromal tumor) and non-GIST origin. This article shows the results of sarcoma experts\' voting on the recommendations presented during the I Ibero-American Consensus on the Management of Peritoneal Sarcomatosis, which took place during the recent celebration of the III Hispanic-Portuguese Meeting for Updates on the Treatment of Sarcomas.
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  • 文章类型: Journal Article
    背景:据报道,细胞减灭术和化疗可改善异时性腹膜转移患者的预后。然而,肿瘤细胞减灭术的腹膜转移类型尚不清楚.因此,我们旨在阐明细胞减灭术有效的病例类别,并报告异时性腹膜转移与细胞减灭术相关的预后.
    方法:本研究纳入了52例连续患者,这些患者在2005年1月至2018年12月期间接受了因结直肠癌引起的异时性腹膜转移的细胞减灭术,并符合选择标准。中位随访期为54.9个月。无复发生存率计算为从异时腹膜转移的细胞减灭术到复发的时间。总生存期定义为从异时腹膜转移的细胞减灭术到死亡或随访期结束的时间。
    结果:5年无复发生存率为30.0%,5年总生存率为72.3%。所有患者均未接受腹腔热化疗。分析表明,5年无复发生存的潜在危险因素。然而,5年总生存率,多变量分析显示,初次手术后<2年(风险比=4.1,95%置信区间=2.0~8.6,p=0.0002)和腹膜转移异时性数量≥3(风险比=9.8,95%置信区间=2.3~42.3,p=0.002)是与不良预后相关的独立因素.
    结论:初次手术后超过2年的长间隔和2个或更少的异时性腹膜转移是结直肠癌异时性腹膜转移细胞减灭术的良好选择标准。
    BACKGROUND: Cytoreductive surgery and chemotherapy reportedly improve the prognosis of patients with metachronous peritoneal metastases. However, the types of peritoneal metastases indicated for cytoreductive surgery remains unclear. Therefore, we aimed to clarify the category of cases for which cytoreductive surgery would be effective and report the prognosis associated with cytoreductive surgery for metachronous peritoneal metastases.
    METHODS: This study included 52 consecutive patients who underwent cytoreductive surgery for metachronous peritoneal metastases caused by colorectal cancer between January 2005 and December 2018 and fulfilled the selection criteria. The median follow-up period was 54.9 months. Relapse-free survival was calculated as the time from cytoreductive surgery of metachronous peritoneal metastases to recurrence. Overall survival was defined as the time from cytoreductive surgery of metachronous peritoneal metastases to death or the end of the follow-up period.
    RESULTS: The 5-year relapse-free survival rate was 30.0% and the 5-year overall survival rate was 72.3%. None of the patients underwent hyperthermic intraperitoneal chemotherapy. The analysis indicated no potential risk factors for 5-year relapse-free survival. However, for 5-year overall survival, the multivariate analysis revealed that time to diagnosis of metachronous peritoneal metastases of < 2 years after primary surgery (hazard ratio = 4.1, 95% confidence interval = 2.0-8.6, p = 0.0002) and number of metachronous peritoneal metastases ≥ 3 (hazard ratio = 9.8, 95% confidence interval = 2.3-42.3, p = 0.002) as independent factors associated with a poor prognosis.
    CONCLUSIONS: Long intervals of more than 2 years after primary surgery and 2 or less metachronous peritoneal metastases were good selection criteria for cytoreductive surgery for metachronous peritoneal metastases from colorectal cancer.
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  • 文章类型: Journal Article
    背景:伴有腹膜转移的胃癌与生存前景降低显著相关。细胞减灭术联合腹腔热化疗(HIPEC)的使用已被证明可以提高这些患者的生存率。尽管取得了这些进步,关于归因于这种治疗方式的生存改善幅度的争论仍然存在.本研究检查了HIPEC后诊断为胃癌和腹膜转移的个体的生存结果,并对细胞学检查结果阳性和阴性的患者进行了比较分析。
    目的:比较HIPEC对腹膜转移和细胞学检查阳性或阴性的胃癌患者生存率的影响。
    方法:在2013年4月至2020年3月之间,在我们机构接受治疗的84例晚期胃癌患者被分为三组:HIPEC(20例腹膜转移患者),细胞学阳性(23例无腹膜结节但冲洗细胞学阳性),细胞学阴性(41例晚期胃癌,无腹膜结节,和阴性洗涤细胞学)。HIPEC队列接受HIPEC胃切除术,而细胞学阳性和细胞学阴性组仅接受胃切除术.人口统计,病态,并比较各组的生存数据。
    结果:HIPEC队列-主要是年轻女性-表现出相对延长的手术持续时间和高失血量。然而,所有三组的并发症发生率一致.HIPEC组的中位生存期为20.00±4.89个月,1年,2年,3年总生存率为73.90%,28.70%,和9.60%,分别。这些数字与细胞学阳性组的生存率(1年时为52.20%,2年时28.50%,和3年时的19.00%)。值得注意的是,47%的患者经历了腹膜复发。
    结论:HIPEC可能对胃癌和腹膜转移患者的短期生存有适度改善,反映细胞学阳性患者的结果。然而,腹膜复发率仍然很高。
    BACKGROUND: Gastric cancer presenting with peritoneal metastasis is notably associated with diminished survival prospects. The use of cytoreductive surgery in conjunction with hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to increase survival rates in these patients. Despite these advancements, debates persist regarding the magnitude of survival improvement attributed to this treatment modality. The present investigation examined survival outcomes following HIPEC in individuals diagnosed with gastric cancer and peritoneal metastasis, and it took a comparative analysis of patients exhibiting positive and negative cytological findings.
    OBJECTIVE: To compare the impact of HIPEC on survival in gastric cancer patients with peritoneal metastasis and positive or negative cytology.
    METHODS: Between April 2013 and March 2020, 84 patients with advanced gastric cancer treated at our institution were categorized into three cohorts: HIPEC (20 patients with peritoneal metastasis), cytology-positive (23 patients without peritoneal nodules but with positive wash cytology), and cytology-negative (41 patients with advanced gastric cancer, no peritoneal nodules, and negative wash cytology). The HIPEC cohort underwent gastrectomy with HIPEC, while the cytology-positive and cytology-negative groups received gastrectomy alone. The demographic, pathological, and survival data of the groups were compared.
    RESULTS: The HIPEC cohort-predominantly younger females-exhibited relatively extended surgical durations and high blood loss. Nevertheless, the complication rates were consistent across all three groups. Median survival in the HIPEC group was 20.00 ± 4.89 months, with 1-year, 2-year, and 3-year overall survival rates of 73.90%, 28.70%, and 9.60%, respectively. These figures paralleled the survival rates of the cytology-positive group (52.20% at 1 year, 28.50% at 2 years, and 19.00% at 3 years). Notably, 47% of patients experienced peritoneal recurrence.
    CONCLUSIONS: HIPEC may offer a modest improvement in short-term survival for patients with gastric cancer and peritoneal metastasis, mirroring the outcomes in cytology-positive patients. However, peritoneal recurrence remained high.
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  • 文章类型: Journal Article
    结直肠肿瘤腹膜转移(PM)的多模式治疗可以改善总生存率(OS)。在这项研究中,我们报道了我们在使用细胞减灭术(CRS)联合腹腔化疗(HIPEC)治疗结直肠肿瘤腹膜转移(PM)方面的经验.第一个目的是评估这些患者的总体生存率。此外,使用Prodige7试验的结果,并将其与熵平衡统计工具相结合,我们生成了一个伪种群,在其上单独测试CRS的使用。我们基于2004年3月至2023年1月期间接受CRS+HIPEC治疗的所有55例患者的前瞻性数据库进行了回顾性分析。中位OS为47个月,1-,3年和5年生存率为90.8%,58.7%和42.7%,分别。使用熵平衡生成的伪群中的数据没有显着差异。这一发现证实了完全细胞减少在实现PM患者的最佳OS中的关键作用。PCI>6似乎是影响OS的最重要的预后因素。目前,CRS+HIPEC似乎是一种治疗策略,可以保证PCI相对较低并且可以实现CCS≤1的患者在OS方面的最佳结果。
    Multimodal treatment in peritoneal metastases (PM) from colorectal neoplasms may improve overall survival (OS). In this study, we reported our experience in using cytoreductive surgery (CRS) combined with intraperitoneal chemohyperthermia (HIPEC) for the treatment of peritoneal metastases (PM) from colorectal neoplasms. The first aim was to evaluate the overall survival of these patients. Furthermore, using the results of the Prodige 7 Trial and incorporating them with the entropy balance statistical tool, we generated a pseudopopulation on which to test the use of CRS alone. We performed a retrospective analysis based on a prospective database of all 55 patients treated with CRS + HIPEC between March 2004 and January 2023. The median OS was 47 months, with 1-, 3- and 5-year survival rates of 90.8%, 58.7% and 42.7%, respectively. There was no significant difference in the data in the pseudogroup generated with entropy balance. This finding confirms the critical role of complete cytoreduction in achieving the best OS for patients with PM. PCI > 6 seems to be the most important prognostic factor influencing OS. At present, CRS + HIPEC seems to be the therapeutic strategy that guarantees the best results in terms of OS for patients with relatively low PCI and in whom a CCS ≤ 1 can be achieved.
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  • 文章类型: Journal Article
    背景:细胞减灭术(CRS)联合腹腔热化疗(HIPEC)是结直肠腹膜癌(CPC)的主要治疗方法。目的是确定接受CRS-HIPEC治疗的CPC患者的无病生存率(DFS)和总生存率(OS)以及与长期生存率(LTS)相关的因素。
    方法:纳入2007年至2021年在HIPEC中心接受CRS-HIPEC的连续CPC患者。计算了实际生存率,和Cox比例风险模型用于识别与OS相关的因素,DFS和LTS。
    结果:有125例CPC患者接受了原发性CRS-HIPEC,平均年龄54.5岁。中位随访时间为31个月。术中平均PCI为11,完全细胞减灭术(CC-0)达到96.8%。中位OS为41.6个月(6-196)。2年和5年OS分别为68%和24.8%,分别,两年DFS为28.8%。与OS较差相关的因素包括HIPEC系统治疗前,同步腹膜外转移,PCI≥20(p<0.05)。CRS-HIPEC之前的进展与更差的DFS相关(p<0.05)。更低的PCI,更少的并发症,较低的复发和较长的DFS与LTS相关(p<0.05).
    结论:CRS和HIPEC可改善CPC患者的OS,但其疾病复发率较高。结果取决于术前治疗反应,腹膜外转移,和腹膜疾病负担。
    BACKGROUND: Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a major treatment of colorectal peritoneal carcinomatosis (CPC). The aim was to determine the disease-free survival (DFS) and overall survival (OS) of patients undergoing CRS-HIPEC for CPC and factors associated with long-term survival (LTS).
    METHODS: consecutive CPC patients who underwent CRS-HIPEC at a HIPEC center between 2007 and 2021 were included. Actual survival was calculated, and Cox proportional hazards models were used to identify factors associated with OS, DFS and LTS.
    RESULTS: there were 125 patients with CPC who underwent primary CRS-HIPEC, with mean age of 54.5 years. Median follow-up was 31 months. Average intraoperative PCI was 11, and complete cytoreduction (CC-0) was achieved in 96.8%. Median OS was 41.6 months (6-196). The 2-year and 5-year OS were 68% and 24.8%, respectively, and the 2-year DFS was 28.8%. Factors associated with worse OS included pre-HIPEC systemic therapy, synchronous extraperitoneal metastasis, and PCI ≥ 20 (p < 0.05). Progression prior to CRS-HIPEC was associated with worse DFS (p < 0.05). Lower PCI, fewer complications, lower recurrence and longer DFS were associated with LTS (p < 0.05).
    CONCLUSIONS: CRS and HIPEC improve OS in CPC patients but they have high disease recurrence. Outcomes depend on preoperative therapy response, extraperitoneal metastasis, and peritoneal disease burden.
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    腹膜假粘液瘤(PMP)是一种惰性恶性综合征。PMP的标准治疗是细胞减灭术加腹腔热化疗(CRS+HIPEC)。然而,高复发率和潜在的临床症状和体征是进一步改善临床结局的主要障碍。此外,由于广泛的腹膜内转移,晚期患者从CRS+HIPEC中获益甚微.PMP治疗的另一个挑战涉及PMP细胞分泌粘液的进行性硬化,通常由于编码鸟嘌呤核苷酸结合蛋白α亚基(GNAS)的基因中的激活突变而增加。因此,迫切需要开发其他PMP疗法。几种免疫相关疗法已经显示出希望,包括使用细菌来源的非特异性免疫原性试剂,放射性免疫治疗剂,和肿瘤细胞衍生的新抗原,但是尚未建立公认的免疫疗法。在这篇综述中,讨论了GNAS突变在促进粘蛋白分泌和疾病发展中的作用。此外,讨论了PMP微环境的免疫学特征和免疫相关治疗,以总结目前对疾病关键特征的理解,并促进免疫疗法的发展.
    Pseudomyxoma peritonei (PMP) is an indolent malignant syndrome. The standard treatment for PMP is cytoreductive surgery combined with intraperitoneal hyperthermic chemotherapy (CRS + HIPEC). However, the high recurrence rate and latent clinical symptoms and signs are major obstacles to further improving clinical outcomes. Moreover, patients in advanced stages receive little benefit from CRS + HIPEC due to widespread intraperitoneal metastases. Another challenge in PMP treatment involves the progressive sclerosis of PMP cell-secreted mucus, which is often increased due to activating mutations in the gene coding for guanine nucleotide-binding protein alpha subunit (GNAS). Consequently, the development of other PMP therapies is urgently needed. Several immune-related therapies have shown promise, including the use of bacterium-derived non-specific immunogenic agents, radio-immunotherapeutic agents, and tumor cell-derived neoantigens, but a well-recognized immunotherapy has not been established. In this review the roles of GNAS mutations in the promotion of mucin secretion and disease development are discussed. In addition, the immunologic features of the PMP microenvironment and immune-associated treatments are discussed to summarize the current understanding of key features of the disease and to facilitate the development of immunotherapies.
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    Introduction and objective: The approach to patients with advanced or metastatic high-grade epithelial ovarian cancer (EOC) has evolved over time with the advent of new therapies and multimodal strategies. The objective of this consensus of experts is to generate national recommendations for the profiling and management of advanced or metastatic high-grade OEC, defined as stages III and IV of the “The International Federation of Gynecology and Obstetrics (FIGO) classification at the time of diagnosis to base on the literature review that included international evidence-based clinical practice guidelines (CPG). Material and methods: Eleven panelists (oncologists and gynecological oncologists) answered 8 questions about the profiling and management of advanced or metastatic ovarian epithelial carcinoma. The panelists were chosen for their academic profile and influence in national health institutions. Guidelines from the “ESMO Standardized Operating Procedures Consensus Conference” were used to develop the consensus. It was agreed that the level of agreement to accept a recommendation should be ≥ 80%. The document was peer reviewed. Results: Eight general recommendations are made, which are presented into five domains. Some of these recommendations are subdivided into specific recommendations. Initial treatment Recommendation 1.1 Complete primary cytoreduction (PCS) surgery is suggested as the initial therapy of choice for patients with high-grade or metastatic EOC, which should ideally be carried out in centers with experience, followed by adjuvant therapy. 1.2 Neoadjuvant chemotherapy followed by interval cytoreduction surgery (ICS) is suggested in those who are unlikely to achieve a complete cytoreduction in PCS either due to unresectable metastatic disease or who present unresectability criteria (imaging, laparoscopic and/or by laparotomy) and that have been defined by a gynecological oncologist and patients with poor functional status and comorbidities according to the criteria of the multidisciplinary team (clinical oncology, gynecological oncology, radiology, etc.). Recommendation 2. In patients with high-grade epithelial ovarian cancer (EOC), in stage III locally advanced or metastatic, who received neoadjuvant chemotherapy and achieved a complete or partial response (cytoreduction with tumor residue < 2.5 mm), the use of Hyperthermic IntraPeritoneal Chemotherapy (HIPEC) could be considered as an alternative to standard platinum-based adjuvant intravenous chemotherapy during interval cytoreductive surgery, after discussion in a multidisciplinary tumor board, at a center experienced in treating this type of patients. Use of genetic testing. Recommendation 3. It is suggested at the time of diagnosis to offer molecular genetic testing to all patients with high-grade advanced or metastatic EOC regardless of family history. Recommendation 4. It is suggested to offer genetic counseling, by qualified personnel, to all patients with high-grade advanced or metastatic EOC who are ordered genetic testing. Recommendation 5. It is suggested that all patients with advanced or metastatic high-grade EOC undergo a germ panel that includes the Breast Cancer Susceptibility Genes 1/2 genes (BRCA 1/2) and the other susceptibility genes according to with institutional protocols and the availability of genetic testing panels; If it is negative, then somatic testing should be performed that includes the homologous recombination deficiency (HRD) status, regardless of family history. Adjuvant Therapy Recommendation 6. 6.1. It is suggested that all patients with advanced stage III/IV EOC, with PSC of (0-2), got adjuvant intravenous chemotherapy as standard treatment within six weeks after Prc. It is suggested paclitaxel/carboplatin. Recommendation 6.2. It is suggested to use standard chemotherapy base on platinum plus Bevacizumab as adjuvant chemotherapy to patients with high-risk disease (EOC stage IV or stage III with suboptimal tumor cytoreduction), following by bevacizumab as maintenance. The use of bevacizumab as maintenance therapy is not recommended if bevacizumab was not included in the first line of treatment. We suggested the dose used in GOG-0218 and ICON7 trials. Recommendation 6.3 It is suggested combined intravenous/intraperitoneal chemotherapy only for selected patients, with optimal cytoreduction (residual lesions < 1 cm), especially those without residual disease (R0) and who are evaluated in a multidisciplinary meeting. It is not considered standard treatment. Recommendation 6.4. 6.4.1 It is suggested to use Poly ADP ribose polymerase (PARP) inhibitors such as olaparib or niraparib as maintenance after receiving first-line chemotherapy in patients with stage III/IV BRCA1/2 positive EOC who received platinumbased chemotherapy and obtained complete response/partial response (CR/PR), 6.4.2 It is suggested to use olaparib alone or in combination with bevacizumab or niraparib in patients with stage III/IV BRCA1/2 positive EOC who received platinum-based chemotherapy plus bevacizumab and achieved CR/PR. 6.4.3 It is suggested to use niraparibin patients with stage III/IV BRCA1/2 negative or unknown EOC who received platinum-based chemotherapy and achieved CR/PR. 6.4.4 It is suggested to use bevacizumab or olaparib plus bevacizumab in patients with EOC stage III/IV BRCA1/2 negative or unknown (HRD positive) who received platinum-based chemotherapy plus bevacizumab and obtained CR/PR. Treatment of disease relapse Recommendation 7. Secondary cytoreductive surgery followed by chemotherapy is suggested for selected patients with high-grade advanced EOC in first relapse, platinum-sensitive (platinum-free interval ≥ 6 months), positive “Arbeitsgemeinschaft Gynäkologische Onkologie – AGO” score or “I-model” positive (< 4.7) with a potential resection to R0 in centers with access to optimal surgical and postoperative support. Note: Platinum-free interval and AGO score have only been developed as positive predictors of complete resection and not to exclude patients from surgery. Recommendation 8. 8.1 For patients with relapse advanced high-grade EOC platinum-sensitive, the following is suggested: Platinum-based combination chemotherapy: carboplatin/liposomal doxorubicin or carboplatin/paclitaxel or carboplatin/nab-paclitaxel or carboplatin/docetaxel or carboplatin/gemcitabine) for six cycles. If combination therapy is not tolerated, give carboplatin or cisplatin alone. Combination chemotherapy (carboplatin/gemcitabine or carboplatin/paclitaxel or carboplatin/doxorubicin liposomal) plus bevacizumab followed by bevacizumab as maintenance (until progression or toxicity). Recommendation 8.2 For patients with relapsed advanced high-grade EOC platinum-resistant, it is suggested: Sequential treatment with chemotherapy, preferably with a non-platinum single agent (weekly paclitaxel or pegylated liposomal doxorubicin or docetaxel or oral etoposide or gemcitabine or trabectidine or, topotecan). Weekly paclitaxel or pegylated liposomal doxorubicin or topotecan could be administrate with or without bevacizumab. Other agents are considered potentially active (capecitabine, cyclophosphamide, ifosfamide, irinotecan, oxaliplatin, pemetrexed, vinorelbine, cyclophosphamide) could be recommended for later lines. Hormone receptor-positive patients who do not tolerate or have no response to cytotoxic regimens may receive hormone therapy with tamoxifen or other agents, including aromatase inhibitors (anastrozole and letrozole) or leuprolide acetate, or megestrol acetate. Patients with a performance score ≥ 3 should be considered only for best supportive care. Recommendation 8.3 Maintenance therapy with PARP inhibitors: It is suggested in patients with relapse advanced high-grade EOC stage III/IV BRCA1/2 (positive, negative or unknown) who have received two or more lines of platinum-based chemotherapy and have achieved CR/PR, use olaparib, niraparib or rucaparib. Niraparib could be useful in BRCA 1/2 +/-/unknown patients, as rucaparib, however, the latter does not yet have approval from the regulatory office in Colombia. Conclusions: It is expected that the recommendations issued in this consensus will contribute to improving clinical care, oncological impact, and quality of life of these women.
    Introducción y objetivo: el abordaje de pacientes con cáncer epitelial de ovario (CEO) de alto grado avanzado o metastásico ha ido evolucionando a través del tiempo con el advenimiento de nuevas terapias y estrategias multimodales. El objetivo de este consenso de expertos es generar recomendaciones nacionales para el perfilamiento y manejo del CEO de alto grado avanzado o metastásico, definido como estadios III y IV de la clasificación de la Federación Internacional de Ginecología y Obstetricia (FIGO) al momento del diagnóstico, a partir de la revisión de la literatura que incluyó guías de práctica clínica (GPC) internacionales basadas en la evidencia. Materiales y métodos: once panelistas (oncólogos y ginecólogos oncólogos) respondieron ocho preguntas sobre el perfilamiento y manejo del carcinoma epitelial de ovario avanzado o metastásico. Los panelistas fueron escogidos por su perfil académico e influencia en instituciones de salud nacionales. Para el desarrollo del consenso se utilizaron los lineamientos de la “Conferencia de consenso de procedimientos operativos estandarizados de ESMO”. Se definió que el nivel de acuerdo para aceptar una recomendación debía ser ≥ 80%. El documento fue revisado por pares. Resultados: Se hacen 8 recomendaciones generales, presentadas en cinco dominios; algunas de ellas se subdividen en recomendaciones específicas. Tratamiento inicial Recomendación 1 1.1. Como terapia inicial de elección para pacientes con CEO de alto grado o metastásico se sugiere la cirugía de citorreducción primaria (Cpr) completa que, idealmente, debe realizarse en centros con experiencia, seguida de terapia adyuvante. 1.2. Se sugiere quimioterapia neoadyuvante seguida de cirugía de citorreducción de intervalo (Cint) en quienes sea improbable alcanzar una citorreducción completa en la Cpr, bien sea por enfermedad metastásica no resecable o que presenten criterios de irresecabilidad (imagenológicos, laparoscópicos o por laparotomía) que hayan sido definidos por un ginecólogo oncólogo. También en pacientes con un pobre estado funcional y comorbilidades de acuerdo con el criterio del equipo multidisciplinario (oncología clínica, ginecología oncológica, radiología, etc.). Recomendación 2. En pacientes con CEO de alto grado, en estadio III localmente avanzado o metastásico, que recibieron quimioterapia neoadyuvante y alcanzaron respuesta completa o parcial (citorreducción con residuo tumoral < 2,5 mm), se podría evaluar el uso de la quimioterapia intraperitoneal hipertérmica (Hyperthermic IntraPeritoneal Chemotherapy - HIPEC) como alternativa a la quimioterapia IV adyuvante estándar basada en platinos durante la Cint, previa discusión en junta multidisciplinaria, en un centro de experiencia en este tipo de pacientes. Uso de pruebas genéticas Recomendación 3. Al momento del diagnóstico, se sugiere ofrecer testeo molecular genético a toda paciente con CEO de alto grado avanzado o metastásico, independientemente de la historia familiar. Recomendación 4. Se sugiere ofrecer asesoramiento genético, por parte de personal calificado, a toda paciente con CEO de alto grado avanzado o metastásico a quien se le ordene un testeo genético. Recomendación 5. Se sugiere que a toda paciente con CEO de alto grado avanzado o metastásico se le realice panel germinal que incluya los genes de susceptibilidad al cáncer de mama 1/2 (BRCA 1/2) y los otros genes de susceptibilidad de acuerdo con los protocolos institucionales y la disponibilidad de paneles de testeo genético; si es negativo entonces se debería realizar testeo somático que incluya el estatus de deficiencia de la recombinación homóloga (homologous recombination deficiency - HRD), independientemente de la historia familiar. Terapia adyuvante Recomendación 6 6.1. Se sugiere que a toda paciente con CEO estadios III/IV avanzado o metastásico, con estatus de desempeño (performance score care - PSC) de 0-2 se le administre como tratamiento estándar quimioterapia intravenosa (IV) adyuvante dentro de las seis semanas posteriores a la Cpr. Se sugiere administrar paclitaxel/carboplatino. 6.2. Se sugiere utilizar quimioterapia estándar basada en platino más bevacizumab como adyuvancia en pacientes con enfermedad de alto riesgo (CEO estadios IV o III con citorreducción tumoral subóptima), continuando con bevacizumab como mantenimiento. No se recomienda el uso de bevacizumab como terapia de mantenimiento si no se incluyó en la primera línea de tratamiento. Se sugiere seguir los esquemas de los estudios Gynecologic Oncology Group Study (GOG-0218) e International Collaborative Ovarian Neoplasm (ICON7). 6.3. Se sugiere la quimioterapia combinada IV/intraperitoneal (IP) solo para pacientes seleccionadas, con una citorreducción óptima (lesiones residuales < 1 cm), en especial aquellas sin enfermedad residual (R0) y que sean evaluadas en junta multidisciplinaria. La quimioterapia combinada IV/IP no se considera como tratamiento estándar. 6.4. 6.4.1. Se sugiere utilizar inhibidores de poli(ADP-ribosa) polimerasa (PARP) tales como olaparib o niraparib como mantenimiento después de recibir una primera línea de quimioterapia en pacientes con CEO estadios III/IV BRCA1/2 positivo que recibieron quimioterapia basada en platino y obtuvieron respuesta completa/respuesta parcial (RC/RP). 6.4.2. Se sugiere utilizar olaparib solo o en combinación con bevacizumab o niraparib en pacientes con CEO estadios III/IV BRCA1/2 positivo que recibieron quimioterapia basada en platino más bevacizumab y obtuvieron RC/RP. 6.4.3. Se sugiere utilizar niraparib en pacientes con CEO estadio III/IV BRCA1/2 negativo o desconocido que recibieron quimioterapia basada en platino y obtuvieron RC/RP. 6.4.4. Se sugiere utilizar bevacizumab u olaparib más bevacizumab en pacientes con CEO estadios III/IV BRCA1/2 negativo o desconocido (HRD positivo) que recibieron quimioterapia basada en platino más bevacizumab y obtuvieron RC/RP. Tratamiento de la recaída de la enfermedad Recomendación 7. Se sugiere la realización de la cirugía de citorreducción secundaria (Csec), seguida de quimioterapia, a pacientes seleccionadas con CEO de alto grado avanzado o metastásico en primera recaída, platino-sensibles (intervalo libre de platinos ≥ 6 meses), puntuación Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) positiva o Integrate model (I-Model) positivo (< 4,7), y con una potencial resección a R0, en centros con acceso a soporte quirúrgico y posoperatorio óptimo. Nota: el intervalo libre de tratamiento con platinos y la puntuación AGO solo se han desarrollado como predictores positivos de resección completa y no para excluir a las pacientes de la cirugía. Recomendación 8 8.1. Para pacientes con CEO de alto grado avanzado o metastásico en recaída platino-sensibles se sugiere: Quimioterapia combinada basada en platino: carboplatino/doxorrubicina liposomal o carboplatino/paclitaxel o carboplatino/ nab-paclitaxel o carboplatino/docetaxel o carboplatino/gemcitabina, por seis ciclos. Si no se tolera la terapia combinada, dar carboplatino o cisplatino solo. Quimioterapia combinada: carboplatino/gemcitabina o carboplatino/paclitaxel o carboplatino/doxorubicina liposomal, más bevacizumab, seguida de bevacizumab como mantenimiento (hasta progresión o toxicidad). 8.2. Para pacientes con CEO de alto grado avanzado o metastásico en recaída, platino-resistentes, se sugiere: Tratamiento secuencial con quimioterapia, preferiblemente con un agente único que no sea un platino (paclitaxel semanal o doxorrubicina liposomal pegilada o docetaxel o etopósido oral o gemcitabina o trabectidina o topotecan). El paclitaxel semanal o la doxorrubicina liposomal pegilada o el topotecan pueden ser administrados con o sin bevacizumab. Existen otros agentes que se consideran potencialmente act ivos (capecitabina, ciclofosfamida, ifosfamida, irinotecán, oxaliplatino, pemetrexed, vinorelbina, ciclofosfamida), que se podrían recomendar para líneas posteriores. Las pacientes con receptores hormonales positivos que no toleran o no tienen respuesta a los regímenes citotóxicos pueden recibir terapia hormonal con tamoxifeno u otros agentes, incluidos los inhibidores de la aromatasa (anastrozol y letrozol) o acetato de leuprolide o acetato de megestrol. Pacientes con PSC ≥ 3 deberían ser consideradas solo para el mejor cuidado de soporte. 8.3. Terapia de mantenimiento con inhibidores PARP. Para pacientes con CEO de alto grado avanzado o metastásico en recaída estadios III/IV BRCA1/2 (positivo, negativo o desconocido), que hayan recibido dos o más líneas de quimioterapia basada en platino y hayan alcanzado RC/RP, se sugiere utilizar olaparib, niraparib o rucaparib. El niraparib podría ser útil en pacientes BRCA 1/2 +/-/desconocido, al igual que el rucaparib, sin embargo, este último no tiene aún aprobación del ente regulador en Colombia. Conclusiones: se espera que las recomendaciones emitidas en este consenso contribuyan a mejorar la atención clínica, el impacto oncológico y la calidad de vida de estas mujeres.
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