Major Postoperative Complications Are a Risk Factor for Impaired Survival after CRS/HIPEC

Schneider, Marcel; Eshmuminov, Dilmurodjon; Lehmann, Kuno

doi:10.1245/s10434-017-5821-7

Cited by 46 publications

(23 citation statements)

References 35 publications

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“…BIOSCOPE B (1-3 risk points) reflects patients with moderate risk factors; these patients are able to reach mCSS of 50 and 39 months respectively, which is equal and above the mCSS of 40 to 45 months reported in recent analyses of patients undergoing CRS/HIPEC. 6,7 BIOSCOPE C patients (4-7 points) profit from CRS/HIPEC with a mCSS of 33 and 25 months, which is clearly superior to the mCSS of 16.9 months in patients with PM treated systemically with modern targeted chemotherapy only. 1 In contrast, BIOSCOPE D patients (!8 points) show a dismal survival of 13 (development) and 7 (validation) months only.…”

Section: Discussionmentioning

confidence: 93%

“…4 Multiple factors influence successful postoperative long-term oncological outcomes, for example, the completeness of resection 5 or the absence of major postoperative complications. 6,7 However, the role of tumor biology and RAS/RAF mutations in the context of PM remains unclear. RAS/RAF proteins work as downstream secondary messengers of the epidermal growth factor receptor (EGFR) which is expressed on 85% of patients with metastatic CRC.…”

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confidence: 99%

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Mutations of RAS/RAF Proto-oncogenes Impair Survival After Cytoreductive Surgery and HIPEC for Peritoneal Metastasis of Colorectal Origin

et al. 2018

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BACKGROUND Adequate selection of patients with peritoneal metastasis (PM) for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) remains critical for successful long-term outcomes. Factors reflecting tumor biology are currently poorly represented in the selection process. The prognostic relevance of RAS/RAF mutations in patients with PM remains unclear. METHODS Survival data of patients with colorectal PM operated in 6 European tertiary centers were retrospectively collected and predictive factors for survival identified by Cox regression analyses. A simple point-based risk score was developed to allow patient selection and outcome prediction. RE-SULTS Data of 524 patients with a median age of 59 years and a median peritoneal cancer index of 7 (interquartile range: 3-12) were collected. A complete resection was possible in 505 patients; overall morbidity and 90-day mortality were 50.9% and 2.1%, respectively. PCI [hazard ratio (HR): 1.08], N1 stage (HR: 2.15), N2 stage (HR: 2.57), G3 stage (HR: 1.80) as well as KRAS (HR: 1.46) and BRAF (HR: 3.97) mutations were found to significantly impair survival after CRS/HIPEC on multivariate analyses. Mutations of RAS/RAF impaired survival independently of targeted treatment against EGFR. Consequently, a simple point-based risk score termed BIOSCOPE (BIOlogical Score of COlorectal PEritoneal metastasis) based on PCI, N-, G-, and RAS/RAF status was developed, which showed good discrimination [development area under the curve (AUC) = 0.72, validation AUC = 0.70], calibration (P = 0.401) and allowed categorization of patients into 4 groups with strongly divergent survival outcomes. CONCLUSION RAS/RAF mutations impair survival after CRS/HIPEC. The novel BIOSCOPE score reflects tumor biology, adequately stratifies long-term outcomes, and improves patient assessment and selection.Background: Adequate selection of patients with peritoneal metastasis (PM) for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) remains critical for successful long-term outcomes. Factors reflecting tumor biology are currently poorly represented in the selection process. The prognostic relevance of RAS/RAF mutations in patients with PM remains unclear. Methods: Survival data of patients with colorectal PM operated in 6 European tertiary centers were retrospectively collected and predictive factors for survival identified by Cox regression analyses. A simple point-based risk score was developed to allow patient selection and outcome prediction. Results: Data of 524 patients with a median age of 59 years and a median peritoneal cancer index of 7 (interquartile range: 3-12) were collected. A complete resection was possible in 505 patients; overall morbidity and 90-day mortality were 50.9% and 2.1%, respectively. PCI [hazard ratio (HR): 1.08], N1 stage (HR: 2.15), N2 stage (HR: 2.57), G3 stage (HR: 1.80) as well as KRAS (HR: 1.46) and BRAF (HR: 3.97) mutations were found to significantly impair survival after CRS/HIPEC on multivariate analyses. ...

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Section: Discussionmentioning

confidence: 93%

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confidence: 99%

Mutations of RAS/RAF Proto-oncogenes Impair Survival After Cytoreductive Surgery and HIPEC for Peritoneal Metastasis of Colorectal Origin

et al. 2018

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“…CRS/HIPEC treatment improves survival of patients with peritoneal metastasis. However, a majority of patients still has recurrent disease within the first two years [26], and future improvements of HIPEC are therefore needed. An interesting finding in our study is the kinetics of WBC during the postoperative course of patients without a complication.…”

Section: Mmentioning

confidence: 99%

Systemic inflammatory response after hyperthermic intraperitoneal chemotherapy (HIPEC): The perfusion protocol matters!

Roth

Eshmuminov

Laminger

et al. 2019

European Journal of Surgical Oncology

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BACKGROUND:: CRS/HIPEC gained acceptance as a treatment for selected patients with peritoneal metastasis. However, the pathophysiology behind HIPEC is poorly understood, and a variety of regimens are currently in use. In this study, we describe for the first-time changes in the postoperative systemic inflammatory reaction, highly different among HIPEC treatment protocols. METHODS:: HIPEC was performed with three protocols, different with regard to perfusion times and drugs: (mito-mycinC/doxorubicin, 90min), (cisplatin, 90min) (oxaliplatin, 30min). Serial blood samples were assessed for C-reactive protein (CRP), white blood cells (WBC), pancreatic stone protein (PSP) and bacterial component (16s rDNA). The study was approved by the local ethics committee and registered at clinicaltirals.gov (NCT02741167). RESULTS:Overall, 140 patients from two European centers were included. In patients without postoperative complications, a secondary peak of inflammatory parameters, CRP (p = 0.015) and PSP (p = 0.004) was observed after HIPEC for 90 min with mitomycinC/doxorubicin or cisplatin but not after 30 min oxaliplatin. In patients after 90 min HIPEC, postoperative serum bacterial 16srDNA level were 2.1 times higher (95% CI 0.646-3.032, p = 0.015) compared to 30 min oxaliplatin. DISCUSSION: In conclusion, we identified a secondary inflammatory reaction after 90 min HIPEC, either with mitomycinC/doxorubicin or cisplatin, not observed after short course HIPEC with oxaliplatin. This protocol dependent physiology of acute phase proteins should be known in the clinical management of patients after HIPEC.

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“…In recent years, the number of centres worldwide that are performing CRS-HIPEC procedures has significantly increased due to improvements in surgical techniques, expansion in the indications and a better understanding of the perioperative care of patients undergoing this procedure. However, the rate of postoperative complications remains high, and they significantly impact the survival of patients [2][3][4]. Only a few large studies have reported on the results of perioperative complications such as acute kidney injury (AKI) [5].…”

Section: Introductionmentioning

confidence: 99%

Identification of risk factors associated with postoperative acute kidney injury after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: a retrospective study

Cata

Zavala

Meter

et al. 2017

International Journal of Hyperthermia

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Major Postoperative Complications Are a Risk Factor for Impaired Survival after CRS/HIPEC

Cited by 46 publications

References 35 publications

Mutations of RAS/RAF Proto-oncogenes Impair Survival After Cytoreductive Surgery and HIPEC for Peritoneal Metastasis of Colorectal Origin

Mutations of RAS/RAF Proto-oncogenes Impair Survival After Cytoreductive Surgery and HIPEC for Peritoneal Metastasis of Colorectal Origin

Systemic inflammatory response after hyperthermic intraperitoneal chemotherapy (HIPEC): The perfusion protocol matters!

Identification of risk factors associated with postoperative acute kidney injury after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: a retrospective study

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