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Clinical Efficacy and Safety of Hyperthermic Intraperitoneal Chemotherapy in Colorectal Cancer Patients at High Risk of Peritoneal Carcinomatosis: A Systematic Review and Meta-Analysis.

ABSTRACT: Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) is an effective measure for improving the prognosis of colorectal cancer (CRC) patients with peritoneal carcinomatosis (PC). However, the role of HIPEC in CRC patients at high risk of PC remains controversial. The current systematic review and meta-analysis aimed to evaluate the clinical efficacy and safety of HIPEC in CRC patients at high risk of PC. Methods: We performed a systematic search of PubMed, Embase, Cochrane Library, and other online databases up to July 30, 2020. The clinical data, including overall survival, disease free survival, peritoneal metastasis rate, and postoperative adverse reaction were screened and analyzed after data extraction. Risk ratios (RRs) were applied to analyze these dichotomous outcomes with a random effects model. Results: A total of 6 available clinical studies involving 603 patients were finally included. CRC patients at high risk of PC who proactively underwent HIPEC treatment showed a significantly reduced peritoneal metastasis rate (RR: 0.41, 95% CI: 0.21-0.83, P = 0.01; I ² = 58%) compared to the similarly high-risk in CRC patients who did not receive HIPEC treatment. However, in terms of overall survival (RR: 1.13, 95% CI: 0.97-1.33, P = 0.12; I ² = 77%), disease-free survival (RR: 1.10, 95% CI: 0.75-1.59, P = 0.63; I ² = 53%), progression free survival (RR: 1.85, 95% CI: 0.48-7.14, P = 0.37; I ² = 93%), and postoperative adverse reactions (RR: 0.1.07, 95% CI: 0.36-3.15, P = 0.90; I ² = 78%), there was no significant difference between the HIPEC treatment and control groups. Conclusions: Proactive HIPEC treatment did not show the expected clinical efficacy in prolonging the overall survival time, disease-free survival time, and progression-free survival time of CRC patients at high risk of PC. However, the preemptive administration of HIPEC was associated with a reduced peritoneal metastasis rate and did not cause adverse additional postoperative effects.

SUBMITTER: Zhao PY

PROVIDER: S-EPMC7705102 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Clinical Efficacy and Safety of Hyperthermic Intraperitoneal Chemotherapy in Colorectal Cancer Patients at High Risk of Peritoneal Carcinomatosis: A Systematic Review and Meta-Analysis.

Zhao Peng-Yue PY Hu Shi-Dong SD Li Yu-Xuan YX Yao Ren-Qi RQ Ren Chao C He Chang-Zheng CZ Li Song-Yan SY Wang Yu-Feng YF Yao Yong-Ming YM Huang Xiao-Hui XH Du Xiao-Hui XH

Frontiers in surgery 20201117

<b>Background:</b> Hyperthermic intraperitoneal chemotherapy (HIPEC) is an effective measure for improving the prognosis of colorectal cancer (CRC) patients with peritoneal carcinomatosis (PC). However, the role of HIPEC in CRC patients at high risk of PC remains controversial. The current systematic review and meta-analysis aimed to evaluate the clinical efficacy and safety of HIPEC in CRC patients at high risk of PC. <b>Methods:</b> We performed a systematic search of PubMed, Embase, Cochrane ...[more]

PMID: 33282908

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Project description:BackgroundBioelectric impedance analysis (BIA)-measured body composition and nutritional status have been used as prognostic indicators in various cancer cohorts. This study investigated whether BIA could provide information on prognosis in peritoneal carcinomatosis patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).MethodsWe retrospectively analyzed the data of 99 patients with preoperative BIA data among those who underwent CRS and HIPEC. The association between BIA-derived parameters and intraoperative peritoneal cancer index (PCI) score was assessed. Predictive analysis for the occurrence of postoperative morbidities including major complications (Clavien-Dindo classification 3-4) and re-admission within 30 days after surgery as well as 1 year mortality was also performed.ResultsBIA-derived mineral (r = 0.224, p = 0.027), fat (r = - 0.202, p = 0.048), and total body water (TBW)/fat-free mass (FFM) (r = - 0.280, p = 0.005) showed significant associations with intraoperative PCI score. Lower TBW/FFM was an independent predictor of major postoperative complications (OR 0.047, 95% CI 0.003-0.749, p = 0.031) and re-admission (OR 0.094, 95% CI 0.014-0.657, p = 0.017) within 30 days after surgery. Higher fat mass was also independently associated with a higher risk of major postoperative complications (OR 1.120, 95% CI 1.006-1.248, p = 0.039) and re-admission (OR 1.123, 95% CI 1.024-1.230, p = 0.013). Intraoperative PCI score > 20 (OR 4.489, 95% CI 1.191-16.917, p = 0.027) and re-admission within 30 days after surgery (OR 5.269, 95% CI 1.288-21.547, p = 0.021) independently predicted postoperative 1-year mortality.ConclusionsWe demonstrate that preoperative BIA-derived TBW/FFM and fat mass were significantly correlated with metastatic extent, assessed by PCI score, in patients with peritoneal carcinomatosis. In addition, BIA-derived TBW/FFM and fat mass showed independent predictability for postoperative 30-day major complications and re-admission in patients undergoing CRS and HIPEC. Our findings suggest that assessment of BIA may improve discrete risk stratification in patients who are planned to receive CRS and HIPEC.

Project description:BackgroundThe peritoneal surface is the second most common site of disease recurrence, after the liver, following definitive surgery for colorectal cancer. Adjuvant intraperitoneal (IP) chemotherapy delivered at time of surgical resection has the potential to delay or prevent future spread to the peritoneal surface and improve clinical outcome. The exact role of adjuvant IP chemotherapy in colorectal cancer, including its associated morbidity and mortality, is not well defined.Study designSystematic review and pooled random effect analysis of comparative trials examining the addition of adjuvant IP chemotherapy compared to surgery alone in colorectal cancer. The primary outcome was overall survival, and the secondary outcomes were of post-operative morbidity and mortality.ResultsIn nine colorectal cancer studies identified, seven were two-arm trials comparing adjuvant IP chemotherapy to surgery alone. Of these, four trials had outcome reporting and met criteria that allowed inclusion into a random effects model. Heterogeneity was measured by Cochran's Q-test (Q = 13.9; p = 0.01) and random effect models were utilised. Pooling eligible trials together revealed a 0.55 odds ratio of death associated with the administration of IP chemotherapy compared to surgery alone (CI = 0.31, 0.98; p = 0.04). Trials selecting patients at elevated risk for the development of peritoneal carcinomatosis by clinicopathological biomarkers for administration of adjuvant IP chemotherapy reported more favourable overall outcomes. There was no increase in mortalities or IP chemotherapy-related abdominal complication rates among patients undergoing IP chemotherapy (OR = 1.4; CI = 0.52, 3.8; p = 0.5).ConclusionsThis systematic review supports the use of adjuvant IP chemotherapy in resectable colorectal cancer at risk for peritoneal spread. Future trials should seek to standardise inclusion criteria and IP chemotherapy modalities to better define the role of this treatment in patients with resectable colorectal cancer.

Project description:BACKGROUND:Patients with peritoneal metastases from colorectal cancer have a poor prognosis. If the intraperitoneal tumour load is limited, patients may be eligible for cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC). This treatment has improved overall survival, but recurrence rates are high. The aim of this study was to create a preclinical platform for the development of more effective intraperitoneal chemotherapy strategies. METHODS:Using organoid technology, five tumour cultures were generated from malignant ascites and resected peritoneal metastases. These were used in an in vitro HIPEC model to assess sensitivity to mitomycin C (MMC) and oxaliplatin, the drugs used most commonly in HIPEC. The model was also used to test a rational combination treatment involving MMC and inhibitors of the checkpoint kinase ATR. RESULTS:MMC was more effective in eliminating peritoneal metastasis-derived organoids than oxaliplatin at clinically relevant concentrations. However, the drug concentrations required to eliminate 50 per cent of the tumour cells (IC50) were higher than the median clinical dose in two of five organoid lines for MMC, and all five lines for oxaliplatin, indicating a general resistance to monotherapy. ATR inhibition increased the sensitivity of all peritoneal metastasis-derived organoids to MMC, as the IC50 decreased 2·6-12·4-fold to well below concentrations commonly attained in clinical practice. Live-cell imaging and flow cytometric analysis showed that ATR inhibition did not release cells from MMC-induced cell cycle arrest, but caused increased replication stress and accelerated cell death. CONCLUSION:Peritoneal metastasis-derived organoids can be used to evaluate existing HIPEC regimens on an individual-patient level and for development of more effective treatment strategies. Surgical relevance Cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) has improved prognosis of patients with peritoneal metastases from colorectal cancer, but disease recurrence is common. More effective and personalized HIPEC is urgently needed. Organoid technology is frequently used for drug screens, as patient-derived organoids can accurately predict clinical therapeutic response in vitro. A panel of organoids was established from peritoneal metastases from colorectal cancer and used to develop a model for testing HIPEC regimens in vitro. Patient-derived organoids differed in sensitivity to commonly used chemotherapeutics, in line with variable clinical outcomes following cytoreductive surgery-HIPEC. Combining MMC with an ATR inhibitor improved the efficacy of MMC. Peritoneal metastasis-derived organoids can be used as a platform to test novel (combination) strategies that increase HIPEC efficacy. In the future, organoids could be used to select patent-tailored HIPEC regimens.

Dataset Information

Clinical Efficacy and Safety of Hyperthermic Intraperitoneal Chemotherapy in Colorectal Cancer Patients at High Risk of Peritoneal Carcinomatosis: A Systematic Review and Meta-Analysis.

Publications

Clinical Efficacy and Safety of Hyperthermic Intraperitoneal Chemotherapy in Colorectal Cancer Patients at High Risk of Peritoneal Carcinomatosis: A Systematic Review and Meta-Analysis.

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