Hyperthermic intraperitoneal chemoperfusion in combined treatment of locally advanced and disseminated gastric cancer: Results of a single-centre retrospective study

Background: Patients with locally advanced gastric cancer (GC) and/or peritoneal metastases have a poor prognosis despite systemic chemotherapy or palliative surgery. The aim of this retrospective comparative non-randomised study was to evaluate aggressive cytoreduction in combination with hyperthermic intraperitoneal chemoperfusion (HIPEC) as a novel treatment strategy for patients with intraperitoneal disseminated and locally advanced GC.

Patients and methods: Forty-nine GC patients with serosal invasion (n?=?19), limited peritoneal metastases (n?=?20), or disseminated peritoneal metastases and tense ascites (n?=?10) underwent combination therapy with HIPEC. Three matched control groups undergoing standard therapies were retrospectively identified.

Results: Combination therapy for serosa-invasive GC reduced the level of metachronous peritoneal carcinomatosis and increased median survival from 12 months to 22.5 months (p?=?0.001). The median and 1-year survival rates for intraperitoneal disseminated GC patients undergoing therapy with the use of HIPEC were 12 months and 68.8% compared with 8 months and 25%, respectively (p?=?0.004) for control subgroup patients (palliative chemotherapy). The symptomatic use of HIPEC allows effective elimination of recurrent ascites in GC patients.

Conclusion: HIPEC is a well-tolerated and effective method of adjuvant therapy for gastric cancer with high risk of intraperitoneal progression. Cytoreduction followed by HIPEC improves survival in patients with limited peritoneal carcinomatosis of gastric origin.     

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal cancer: survival outcomes and patient selection

Background

Chemotherapy hyperthermic intraperitoneal chemotherapy (HIPEC) is playing an ever increasing role in the management of colorectal cancer (CRC) with peritoneal metastases (PM) as results approach those of surgical resection of liver metastases. Selection criteria for treatment type, sequence and timing of currently available therapies remain ill-defined.

Methods

We review the current published literature analyzing outcomes by treatments with surgery, systemic chemotherapy, cytoreductive surgery (CRS) and HIPEC, and ongoing clinical trials. A clinical pathway that incorporates all currently available therapies, determining the timing and sequence of such therapies was constructed.

Results

Most of the literature on outcome data comes from studies reporting the results of CRS and HIPEC with large series showing a median survival of 32-47 months. Meanwhile, the vast majority of patients, over 90% in the United States, are being treated with palliative systemic therapies following the NCCN guidelines.

Conclusions

Cooperation between medical and surgical oncologists represents an unmet need in oncology when it comes to patients with CRC with PM. The presented clinical pathway constitutes a feasible and much needed first step to start this cooperation.     

细胞减灭术联合腹腔热灌注化疗治疗胃癌腹膜转移的系统评价

目的:系统评价细胞减灭术(cytoreductive surgery,CRS)联合腹腔热灌注化疗(hyperthermic intraperitoneal chemotherapy,HIPEC)治疗胃癌伴腹膜转移患者的临床有效性和安全性,为临床应用与深入研究提供参考.方法:计算机检索PubMed、Cochrane图书馆、EMbase、MEDLINE(Ovid)、CNKI、维普中刊数据库、中国生物医学文献数据库,收集利用CRS联合HIPEC治疗胃癌伴腹膜转移患者的所有研究,包括随机对照试验(randomized controlled trail,RCT)和非随机对照试验(non-randomized controlled trail,非RCT),对纳入研究主要从生存期和安全性两方面进行统计分析.结果:纳入1项RCT和8项非RCT,共504例患者.生存期方面,RCT中,CRS联合HIPEC组的中位生存期为11个月,明显高于单纯CRS组的7个月(P=0.003).8项非RCT中,CRS联合HIPEC治疗的1、2、3年合计总体生存率分别为52.9%、27.1%、16.8%.手术切除程度达到CC 0~1分是预后较好的预测指标.安全性方面,非RCT显示联合治疗方案围手术期总体死亡率为4.8%,严重并发症的合计发生率为24.9%,在RCT中这两项数据分别为0和13.1%.结论:对于胃癌伴腹膜转移,尤其是达到CC 0~1切除的患者,CRS联合HIPEC能延长患者的生存期,但同时存在较高的严重并发症发生率.     

细胞减灭术+腹腔热灌注化疗治疗腹膜假黏液瘤——单中心854例经验总结

目的:腹膜假黏液瘤(pseudomyxoma peritonei,PMP)是一种罕见的临床综合征,细胞减灭术(cytoreductive surgery,CRS)联合腹腔热灌注化疗(hyperthermic intraperitoneal chemotherapy,HIPEC)因其良好的治疗效果已经成为各中心公认的标准治疗方案,航天中心医院从2008年开始致力于PMP患者诊治工作,2016年开始将全腹膜切除应用于临床,本研究通过对既往资料进行收集整理,对PMP治疗经验进行总结。方法:回顾分析2008年1月到2019年1月航天中心医院腹膜假黏液瘤中心收治并接受手术治疗的PMP患者临床资料及随访结果。对所有患者的手术方式、根治程度及并发症发生情况等临床资料进行搜集整理,并通过随访结果对相关因素进行生存分析,了解CRS+HIPEC在PMP治疗中的临床价值,同时对腹膜切除技术治疗效果进行评价。结果:共纳入854例患者,平均年龄50岁,中位改良腹膜肿瘤指数(peritoneal cancer index,PCI)为29,其中25.5%的患者接受了根治性手术切除,细胞减灭程度(completene...     

完全肿瘤细胞减灭术加腹腔热灌注化疗治疗胃癌腹膜转移的病例筛选策略

目的:构建肿瘤细胞减灭程度(completeness of cytoreduction,CC)预测模型,为肿瘤细胞减灭术(cytoreductive surgery,CRS)加腹腔热灌注化疗(hyperthermic intraperitoneal chemotherapy,HIPEC)治疗胃癌腹膜转移(gastric cancer with peritoneal metastasis,GCPM)提供病例筛选方法。方法:比较完全CRS(complete CRS,CCRS)组和不完全CRS(incomplete CRS,ICRS)组患者基本临床病理特征和治疗参数,通过逻辑回归模型筛选CC独立预测因子,精准预测CCRS可能性。结果:125例患者纳入本研究,其中CC0组52例(41.6%),中位总生存期为30.0(95%CI:16.8～43.3)个月;CC1-3组73例,中位总生存期7.3(95%CI:5.7～8.8)个月,差异有统计学意义(P<0.001),而CC1、CC2和CC3组间中位总生存期差异无统计学意义(P>0.05)。因此,CC0定义为CCRS组,CC1-3定义为I...     

Oxaliplatin-based hyperthermic intraperitoneal chemotherapy with single drug versus multiple drug treatment for colorectal cancer with peritoneal metastases: an observational cohort study

BackgroundLong-term survival for selected patients with peritoneal metastases (PM) from colorectal cancer (CRC) is possible when treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The objective of this study was to compare three different oxaliplatin-based (OX)-HIPEC regimens. Primary end-point was disease-free survival (DFS), and secondary endpoints, morbidity and overall survival (OS).MethodsThis is a retrospective study of all patients with colorectal PM treated with CRS and HIPEC between 2004 and 2015 from the prospectively maintained Uppsala HIPEC database. One hundred and thirty-three patients were identified. Three HIPEC regimens were included: OX-HIPEC, OX-HIPEC + post-operative intraperitoneal chemotherapy (EPIC) with 5-fluorouracil (5-FU), and oxaliplatin-irinotecan-based (OXIRI)-HIPEC. Multivariable Cox regression for DFS was performed.ResultsSixty-one patients received OX-HIPEC, 24 patients received OX-HIPEC + 5-FU EPIC, and 48 patients received OXIRI-HIPEC. The DFS for the OX-HIPEC group was 10.5 months, OX-HIPEC + EPIC 11.9 months, and OXIRI-HIPEC 13.4 months (OX-HIPEC vs. OXIRI HIPEC, P=0.049). The morbidity and OS did not differ between the groups. In the multivariable analysis, low peritoneal cancer index (PCI), absence of liver metastases, low completeness of cytoreduction (CC) score, and multiple drug (EPIC or OXIRI) HIPEC regimen were independent prognostic factors for DFS.ConclusionsThis study showed improved DFS with an intensification of HIPEC by adding irinotecan or EPIC compared to oxaliplatin alone without an increase in morbidity or mortality.     

Clinical efficacy of cytoreductive surgery and hyperthermic chemotherapy in peritoneal carcinomatosis from gastric cancer

Evaluation of: Yang XJ, Huang CQ, Suo T et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer: final results of a Phase III randomized clinical trial. Ann. Surg. Oncol. 18(6), 1575–15781 (2011).

Peritoneal carcinomatosis (PC) is the most common pattern of metastasis and recurrence in patients with gastric cancer and is associated with poor clinical outcome and survival. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) was recently established as a new treatment option for PC of gastrointestinal cancer. However, the role of cytoreductive surgery in gastric cancer and the intrinsic role of HIPEC remains unclear. The evaluated article presented a single center Phase III study, randomizing 68 patients with PC from gastric cancer to surgical cytoreduction only (CRS; n = 34) versus cytoreduction plus HIPEC with cisplatin and mitomycin (CRS+HIPEC; n = 34). Median overall was 6.5 months in the CRS group and 11.0 months in the CRS+HIPEC group (p = 0.046). Serious adverse events were acceptable in both groups. Multivariate analysis found CRS+HIPEC, synchronous PC, complete cytoreduction, systemic chemotherapy >6 cycles and no incidence of severe adverse events independent predictive factors for survival. This was the first study to show the positive effects of HIPEC in addition to CRS in PC independently of the tumor entity. In patients with gastric cancer, multimodal treatment concepts combining surgical cytoreduction and HIPEC may provide a new option in carefully selected patients.     

Laparoscopic distal gastrectomy and hyperthermic intraperitoneal chemotherapy in the treatment of advanced gastric cancer: a retrospective case-matched study on perioperative outcomes

BackgroundThis study aimed to assess the safety and efficacy of laparoscopic distal gastrectomy (LDG) with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced gastric cancer (AGC).MethodsIn this case-matched study, we retrospectively reviewed the database of 223 patients with AGC who underwent LDG in Tangdu Hospital from April 2016 to February 2019. Among all participants, 177 patients underwent LDG alone and 46 underwent LDG with HIPEC. We matched total of 138 (1:2) patients from the LDG + HIPEC group (n 46) and the LDG group (n 92) for gender, age, date of operation, and tumor-node-metastasis (TNM) stage of tumor.ResultsThere was no significant difference in the Clavien-Dindo classification of complications between LDG alone and LDG + HIPEC patients. Further analysis showed the morbidity of gastroparesis to be significantly increased in LDG + HIPEC patients. At the same time, we found that the operation time, the time to 1st flatus, and hospital stay were longer in LDG + HIPEC patients and the incidence of abdominal recurrence 2 years after operation was significantly higher in the LDG group than the LDG + HIPEC group.ConclusionsThe combination of LDG with intraoperative HIPEC is a safe and feasible method for AGC and HIPEC will limit the recovery of gastrointestinal functions. In addition, during the follow-up of our study, although there was no statistical difference between the two groups in abdominal recurrence at 2 years after surgery, a decreasing trend of abdominal recurrence in LDG + HIPEC patients could be seen in comparison to LDG patients.     

Repeat cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: review of indications and outcomes

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is an established treatment option in selected patients with peritoneal dissemination from a variety of epithelial primaries. Even though a small proportion will be alive and potentially cured at 10 years, the majority will eventually develop recurrent disease. Repeat CRS/HIPEC is a valid consideration in a selected subpopulation of patients with isolated peritoneal recurrence. This review summarizes the data on patient selection, feasibility, limitations and outcomes of repeat CRS/HIPEC.     

减瘤术联合术中腹腔内温热化疗治疗消化道肿瘤腹膜转移

消化道恶性肿瘤腹膜转移在临床十分常见,预后极差。近年来,减瘤术联合术中腹腔内温热化疗方案治疗效果满意。现综述如下。     

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for the treatment of advanced epithelial and recurrent ovarian carcinoma: a single center experience

Background: With standard treatment of epithelial ovarian cancer (EOC), prognosis is very poor. The aim of this study is to show early and late results in patients who underwent cytoreductive surgery and intraperitoneal chemotherapy.

Patients and methods: This was a retrospective single centre study. All patients with advanced and recurrent ovarian cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) or modified early postoperative intraperitoneal chemotherapy (EPIC) were included in the study.

Results: In the period 1995–2014, 116 patients were treated, 55 with primary EOC and 61 with recurrent EOC. The mean age was 59 years (26–74). Statistically, median survival time was significantly longer in the group with primary advanced cancer of the ovary (41.3 months) compared to relapsed ovarian cancer (27.3 months). Survival for the primary EOC was 65 and 24% at 3 and 5 years, respectively. Survival for recurrent EOC was 33 and 16% at 3 and 5 years, respectively. Mortality was 1/116 (0.8%). Morbidity was 11/116 (9.5%). Peritoneal cancer index (PCI) was ≤20 in 59 (51%) patients and statistically, their average survival was significantly longer than in the group of 57 (49%) patients with PCI?>20 (p?=?0.014).

Conclusions: In advanced or recurrent EOC, a curative therapeutic approach was pursued that combined optimal cytoreductive surgery and intraperitoneal chemotherapy. PCI and timing of the intervention (primary or recurrent) were the strongest independent prognostic factors.     

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in treatment of gastric cancer with peritoneal carcinomatosis

Although gastric cancer with peritoneal carcinomatosis is associated with poor prognosis and is generally treated with palliative systemic therapy,recent studies have shown that cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may prove to be an efficacious treatnent option.In addition to reviewing the natural history of gastric cancer with peritoneal carcinomatosis,this mini-review examines literature on the efficacy of CRS and HIPEC as compared to chemotherapy and surgical options.Both randomized and nonrandomized studies were summarized with the emphasis focused on overall survival.In summary,CRS and HIPEC are indeed a promising treatment option for gastric cancer with peritoneal carcinomatosis and large randomized clinical trials are warranted.     

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for treatment of ovarian cancer

Hyperthermic intraperitoneal chemotherapy (HIPEC), a strategy combining maximal cytoreductive surgery and maximal regional chemotherapy, has been applied to treat ovarian cancer resulting in long-term survival rates in selected patients. However, the status of HIPEC in ovarian cancer remains an experimental procedure, given the many variables among the data and trials reviewed, to enable us to derive strong conclusions about its role from this overview. In this review we discuss treatment with HIPEC in patients with ovarian cancer and future prospective of its use in clinical setting. HIPEC is an effective tool in the treatment of selected patients with peritoneal carcinomatosis from ovarian cancer. Unfortunately, due to the lack of randomised trials, the evidence of HIPEC is very limited. Future randomised studies are awaited to define the role and clinical impact of HIPEC in ovarian cancer.     

细胞减灭术联合腹腔热灌注化疗治疗恶性腹膜间皮瘤20例分析

  目的  探讨肿瘤细胞减灭术（cytoreductive surgery,CRS）联合腹腔热灌注化疗（hyperthermic intraperitoneal chemotherapy,HIPEC）治疗恶性腹膜间皮瘤（malignant peritoneal mesothelioma,MPM）的围手术期安全性及其疗效。  方法  回顾性分析2015年1月至2020年6月于航天中心医院接受治疗的20例MPM患者的临床病理资料,评价CRS+HIPEC治疗模式安全性,通过单因素及多因素统计分析研究影响患者生存的预后因素。  结果  20例患者中男性8例,女性12例,男女比例为:1:1.5。病理结果均为MPM,病理分型为上皮型。接受CRS+HIPEC治疗后总体1、2、3年生存率分别为73.9%、58.2%和43.6%,其中肿瘤细胞减灭程度（completeness of cytoreduction,CC）达到0/1的患者3年生存率为75%。单因素分析结果显示,性别（P=0.295）,CA125异常（P=0.256）,既往手术（P=0.460）以及静脉化疗（P=0.283）未见对总生存有显著影响。而年龄 > 60岁（P=0.037）,CC-2/3（P=0.027）,腹膜癌指数（peritoneal cancer index,PCI）≥20分（P=0.014）为预后不良的危险因素。  结论  MPM是一种罕见疾病,早期诊断困难,传统治疗预后差,静脉化疗无法有效改善预后。尽早行CRS+HIPEC综合治疗安全可靠,可以明显延长患者生存。      

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from colorectal cancer: A case‐control study from a Chinese center

Background

Advanced colorectal cancer (CRC) is prone to developing peritoneal carcinomatosis (PC). This case‐control study was to compare the efficacy and safety of cytoreductive surgery (CRS) versus CRS plus hyperthermic intraperitoneal chemotherapy (HIPEC) in Chinese patients with CRC PC.

Methods

The 62 consecutive PC patients were treated with CRS (Control group, n = 29) or CRS + HIPEC (Study group, n = 33). The primary end point was overall survival (OS), the secondary end points were perioperative safety profiles.

Results

For the comparison of Control versus Study groups, the peritoneal cancer index (PCI) ≤20 was 13 (44.8%) versus 16 (48.5%) patients (P = 0.78), complete cytoreduction (CC0‐1) was achieved in 9 (31.0%) versus 14 (42.4%) cases (P = 0.36). At the median OS was 8.5 (95% confidence interval [CI] 4.7–12.4) versus 13.7 (95% CI 10.0–16.5) months (P = 0.02), the 1‐, 2‐, and 3‐year survival rates were 27.5% versus 63.6%, 12.0% versus 20.0%, and 0.0% versus 16.0%, respectively. Serious adverse events in postoperative 30 days were 9.4% versus 28.6% (P = 0.11). Multivariate analysis revealed that CRS + HIPEC, CC0‐1, adjuvant chemotherapy ≥6 cycles were independent factors for OS benefit.

Conclusion

CRS + HIPEC could improve OS for CRC PC patients, with acceptable perioperative safety. J. Surg. Oncol 2014; 109:730–739. © 2013 The Authors. Journal of Surgical Oncology. Published by Wiley Periodicals, Inc.     

Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy for the treatment of primary peritoneal serous carcinoma: Results of a Chinese retrospective study

Purpose Primary peritoneal serous carcinoma (PPSC) is a rare condition with a poor survival rate, even after treatment with debulking surgery followed by systemic chemotherapy. This study evaluated the efficacy and safety of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of PPSC.

Patients and methods This retrospective study included 22 female patients with primary advanced PPSC (group A, n?=?12) or recurrent PPSC (group B, n?=?10) treated with 25 CRS?+?HIPEC procedures. The primary end point was overall survival (OS), and the secondary end points were safety profiles.

Results A total of 25 CRS?+?HIPEC procedures were performed in these 22 patients. The median OS was 31.0 months (95% confidence interval (CI) 22.3–39.7), and the 1-, 3-, and 5-year survival rates were 100%, 45.5%, and 27.3%, respectively. Subgroup analyses revealed that the median OS was 31.0 months (95% CI 19.8–42.2) for group A vs. 38.5 months (95% CI 9.6–67.4) for group B (P?=?0.832, log rank test); 51.5 months (95% CI 34.9–68.1) for peritoneal cancer index (PCI)?≤?15 vs. 20.3 months (95% CI 12.6–28.0) for PCI > 15 (P?=?0.000, log rank test); and 38.5 months (95% CI 22.5–54.5) for completeness of cytoreduction (CC) of 0–1 vs. 23.5 months (95% CI 15.3–31.7) for CC of 2–3 (P?=?0.178, log rank test). There were no perioperative deaths. Serious adverse events (SAEs) occurred in two patients (9.1%). A univariate analysis identified PCI ≤ 15 as the only prognostic predicator (hazard ratio (HR) 13.1, 95% CI 2.7–63.4, P?=?0.001).

Conclusions CRS?+?HIPEC could contribute to favourable outcomes for select PPSC patients with acceptable safety profiles.