Ann Surg Oncol DOI 10.1245/s10434-015-4892-6
ORIGINAL ARTICLE – COLORECTAL CANCER
Predictors of Severe Morbidity After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Patients With Colorectal Peritoneal Carcinomatosis Geert A. Simkens, MD, Thijs R. van Oudheusden, MD, Misha D. Luyer, MD, PhD, Simon W. Nienhuijs, MD, PhD, Grard A. Nieuwenhuijzen, MD, PhD, Harm J. Rutten, MD, PhD, FRCS, and Ignace H. de Hingh, MD, PhD Department of Surgical Oncology, Catharina Hospital, Eindhoven, The Netherlands
ABSTRACT Background. Severe morbidity after cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is, besides the obvious short-term consequences, associated with impaired long-term outcomes. The risk factors for severe morbidity in patients with peritoneal carcinomatosis (PC) of colorectal origin are poorly defined. This study aimed to identify risk factors for severe morbidity after CRS ? HIPEC in patients with colorectal PC. Methods. Patients with colorectal PC who underwent CRS ? HIPEC between 2007 and 2015 were categorized and compared between those with and those without severe morbidity. Risk factors were identified using logistic regression analysis. Morbidity was graded according to the Clavien–Dindo classification, with grade 3 or higher indicating severe morbidity. Results. This study included 211 patients, of whom 53 patients (25.1 %) experienced morbidity of grade 3 or higher. The identified risk factors for severe morbidity were extensive prior surgery [odds ratio (OR) 4.3], a positive recent smoking history (OR 4.0), a poor physical performance status (OR 2.9), and extensive cytoreduction (OR 1.2 per additional resection). Patients with a greater number of risk factors more often had severe morbidity and higher reoperation, readmission, and mortality rates.
Electronic supplementary material The online version of this article (doi:10.1245/s10434-015-4892-6) contains supplementary material, which is available to authorized users. Ó Society of Surgical Oncology 2015 First Received: 19 June 2015 I. H. de Hingh, MD, PhD e-mail:
[email protected]
Furthermore, an internally validated preoperative prediction model for severe morbidity with an area under the curve of 70 % was constructed. Conclusion. The current study identified risk factors for severe morbidity after CRS ? HIPEC in patients with colorectal PC. Patients with a combination of risk factors have a substantial risk of severe morbidity and therefore should be carefully selected for CRS ? HIPEC. The preoperative decision model can be a valuable additional tool in this process of patient selection.
Cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is considered the standard treatment for selected patients with limited peritoneal carcinomatosis (PC) of colorectal origin.1 In the early years of this procedure, high treatment-related morbidity and mortality were a major concern. However, more recent studies report decreased rates of postoperative morbidity (30 %) and mortality (3 %).2 This decrease is primarily attributed to better patient selection and increased experience with peritoneal surface surgery. Recently, severe postoperative complications have been associated with decreased overall and disease-free survival after CRS ? HIPEC.3,4 Moreover, postoperative complications are a burden for both patients and their relatives in terms of impaired quality of life and for society in terms of financial costs.5,6 Therefore, prevention of complications after CRS ? HIPEC remains an important challenge. To minimize the risk of morbidity, several factors associated with postoperative complications have already been identified. However, most of the available prognostic studies describe heterogeneous groups of patients with different origins of PC such as appendiceal pseudomyxoma peritoneı¨ and peritoneal mesothelioma.7–9 These diseases can be considered as different entities with major variations
G. A. Simkens et al.
in the extent of peritoneal disease as well as complete macroscopic cytoreduction rates and therefore require different surgical techniques with their specific postoperative morbidities.10,11 Furthermore, the percentage of colorectal patients included in the largest prognostic study to date was only 5 %. Consequently, risk factors for severe morbidity after CRS ? HIPEC for patients with PC of colorectal origin still are poorly defined. This underscores the need for better prediction tools to identify patients at risk for severe morbidity after this extensive colorectal procedure. Therefore, this study aimed to identify risk factors associated with severe morbidity after CRS ? HIPEC for patients with colorectal PC. Additionally, a preoperative prediction model was constructed, which can be of value in predicting a specific subset of patients at high risk for severe morbidity after CRS ? HIPEC. METHODS Patients Patients with colorectal PC who underwent CRS ? HIPEC with (R2a/CC-1: B2.5 mm) or without (R1/CC-0) minimal macroscopic residual disease between July 2007 and January 2015 in the Catharina Hospital Eindhoven were included in this study. Relevant patient, tumor, and treatment-related characteristics were collected in a prospective database. The medical ethical committee of the Catharina Hospital Eindhoven approved this study. The patients were divided into two groups based on whether they experienced severe postoperative complications or not. These patients were staged according to the Clavien–Dindo Classification of Surgical Complications.12 Severe complications were defined as complications with a Clavien–Dindo stage of 3 or higher, indicating a complication requiring a surgical, radiologic, or endoscopic intervention or admission to intensive care. Follow-up care for postoperative complications was complete until 90 days after CRS ? HIPEC because postoperative complications also occur beyond the 30-day postoperative period.13 The extent of peritoneal disease was assessed with the peritoneal cancer index (PCI) score. Other relevant definitions of scoring systems and comorbidities are given in the online-only methods section. CRS ? HIPEC The CRS ? HIPEC procedure was performed as described in detail in the online-only methods section by a specialized surgical team that performed approximately 350 CRS ? HIPEC procedures for different indications during
the study period.14 Colorectal PC patients were considered eligible for CRS ? HIPEC if they had an Eastern Cooperative Oncology Group (ECOG) performance status of 3 or lower and a PCI score of 20 or lower, although occasionally a higher PCI score was accepted for young and motivated patients. Patients with other systemic metastases, except for three or fewer resectable liver metastases, were excluded from treatment with CRS ? HIPEC. Furthermore, the procedure was terminated if no complete or near-complete macroscopic cytoreduction was possible or if such a large portion of the small bowel was affected that proper resection would have resulted in short bowel syndrome. In the current study, neoadjuvant systemic chemotherapy was not the standard of care for patients treated with CRS ? HIPEC. Nevertheless, approximately 20 % of the patients were treated with systemic chemotherapy before CRS ? HIPEC in case of a nonresectable primary tumor or excessively extensive peritoneal disease. After neoadjuvant treatment, patients were restaged and reevaluated for CRS ? HIPEC. According to protocol, patients were treated with adjuvant systemic chemotherapy after CRS ? HIPEC if their physical status allowed such systemic treatment. Statistical Analysis Statistical analyses were performed using SPSS, version 21.0 (IBM Corporation, Armonk, NY, USA). Binary and categorical variables are expressed as n (%) and were analyzed using Chi square or Fisher’s exact test if more than 20 % of the cells had an expected count of \5. Continuous variables are expressed as mean ± standard deviation (SD) or median (range) and were analyzed using a Student’s t test or the Mann–Whitney U test, depending on their distribution. All tests were performed in a twosided manner, and a p value lower than 0.05 was considered to indicate statistical significance. To identify overall risk factors for severe morbidity, univariate analysis of all relevant patient, tumor, and treatment characteristics was performed. Consequently, all univariate statistically significant and noncorrelating variables without missing values were included in a binary logistic regression model. To construct a preoperative prediction model for severe morbidity, all preoperatively known risk factors were entered into a multivariate regression model. This model was internally validated by bootstrap resampling with RStudio (http://www.rstudio.com, version 0.99.441; RStudio Inc., Boston, MA, USA), with addition of the Regression Modeling Strategies (rms) package.15 Bootstrapping is a method in which sampling, model building, and evaluation are repeated multiple times.16 This method
Risk Factors for Morbidity after HIPEC
corrects for overoptimism of the original model by providing a shrinkage factor. Shrinkage of the regression coefficients aims to improve predictions for future patients. Subsequently, the corrected model was used to calculate risk percentages and 95 % confidence intervals (CI’s) for patients according to their risk factors. The overall performance of this model was assessed with the (scaled) Brier-score (0 representing a perfect model and 0.25 representing a noninformative model if the mean event rate is 50 %).17 The discriminative ability of this model was assessed with the area under the receiving operating characteristic (ROC) curve.
analysis, the independent risk factors for severe morbidity continued be a PSS higher than 1 [odds ratio (OR), 4.29; 95 % CI 1.70–10.83], a positive recent history of smoking (OR 3.99; 95 % CI 1.75–9.10), an ECOG score higher than 1 (OR 2.89; 95 % CI 1.31–6.35), and a greater number of resections during CRS ? HIPEC (OR 1.21; 95 % CI 1.02– 1.45 for each additional resection). The PCI score was not significant in the multivariate analysis and therefore was not identified as an independent risk factor for severe morbidity (OR 1.04; 95 % CI 0.96–1.12).
RESULTS
The patients were stratified according to their number of risk factors (Table 3; Fig. 1). The risk of severe postoperative complications was 5.3 % for the patients without any risk factors. Patients with one, two, three, or four risk factors had chances of 14.7, 29.3, 66.7, or 100 %, respectively, for the development of severe postoperative complications. This trend also was reflected in the reoperation rate, intensive care unit stay, hospital stay, and readmission rate, all of which increased if more risk factors were present.
In this study, 211 patients with colorectal PC underwent CRS ? HIPEC. The median age in this group was 62.9 years (range 24.3–80.7 years), and 51.7 % of the patients were women. At least one comorbidity was present in 118 patients (55.9 %), and 17 patients (8.1 %) had an American Society of Anesthesiologists (ASA) score of 3. The median PCI score was 8 (range 1–25), and complete macroscopic (R1) cytoreduction was achieved for 93.8 % of the patients.
Postoperative Outcomes According Risk Factors
Preoperative Risk Assessment of Severe Morbidity Univariate Analysis Severe postoperative complications developed in 53 patients (25.1 %) after CRS ? HIPEC. The univariate analysis showed that a prior surgical score (PSS) higher than 1 (p = 0.048), an ECOG score higher than 1 (p = 0.002), a positive recent history of smoking (p \ 0.001), and pulmonary comorbidity (p = 0.001) were significantly associated with the development of severe morbidity (Table 1). The median PCI score (9; range 3–23 vs 7; range 1–25; p = 0.008) and the median number of visceral resections (2; range 0–6 vs 1; range 0–6; p = 0.016) were significantly higher in the group of patients with severe postoperative complications. Furthermore, the total number of resections during CRS ? HIPEC was higher in the group with severe postoperative complications (6; range 0– 11 vs 4; range 0–12; p = 0.009). This also was reflected in a higher median amount of intraoperative blood loss in this group (1000 ml; range 100–6400 ml vs 700 ml; range 100–6600 ml; p = 0.035; Table 2). Risk Factors for Severe Morbidity Two different multivariate analyses were performed: one to identify overall risk factors for severe postoperative complications and another to build a preoperative prediction model for severe morbidity. After the first multivariate
In addition, to estimate the preoperative risk for severe postoperative complications, all three preoperatively identified risk factors (PSS [1, a positive smoking history, and an ECOG score [1) were included in a predictive model (Table 4). Internal validation by bootstrapping (n = 1000) resulted in a shrinkage factor of 0.948. After correction of the regression coefficients, the area under the ROC curve was 70 %, representing acceptable discriminative ability of this model. Additionally, the Brier score was 0.172 and the scaled Brier score was 0.088, representing good overall performance of the model. This model can be used as an additional preoperative tool to assess the probability of severe morbidity developing after CRS ? HIPEC (Fig. 2). The percentages of patients with severe morbidity and corresponding 95 % CI’s based on three preoperative risk factors are shown. DISCUSSION Recently, two studies identified severe morbidity after CRS ? HIPEC as an important negative prognostic factor for both overall and disease-free survival in patients with colorectal PC.3,4 Similar findings have been found for nonmetastasized colorectal surgery, in which surgical-site infections were associated with impaired long-term survival.18 Furthermore, a recent meta-analysis identified
G. A. Simkens et al. TABLE 1 Univariate analysis of preoperatively identified characteristics of colorectal PC patients undergoing cytoreduction and HIPEC Variable
Severe morbidity (Clavien–Dindo C3) Yes (N = 53)
p value No (N = 158)
n
%
n
%
Gender Male
24
(45.3)
78
(49.4)
Female Age (median [range])
29 64.8 [24–77]
(54.7)
80 62.4 [31–81]
(50.6)
BMI (mean ± SD)
25.3 ± 4.4
0.607 0.329
26.1 ± 4.3
0.216
ASA score 1
5
(9.4)
19
(12.0)
2
44
(83.0)
126
(79.7)
3
4
(7.5)
13
(8.2)
B1
9
(17.0)
49
(31.0)
[1
44
(83.0)
109
(69.0)
B1
34
(64.2)
133
(84.2)
[1
19
(35.8)
25
(15.8)
0.856
Prior surgical score 0.048
ECOG performance status 0.002 \0.001
Positive recent history of smoking
19
(35.8)
22
(13.9)
Recent alcohol consumption
23
(43.4)
68
(43.0)
0.964
Cardiovascular comorbidity Pulmonary comorbidity
26 12
(49.1) (22.6)
68 10
(43.0) (6.3)
0.446 0.001
Diabetes mellitus
10
(18.9)
17
(10.8)
0.126
Overall comorbidity
35
(66.0)
83
(52.5)
0.087
Synchronous
27
(50.9)
94
(59.5)
0.276
Metachronous
26
(49.1)
64
(40.5)
Right colon
23
(43.4)
58
(36.7)
Transverse colon
4
(7.5)
11
(7.0)
Left colon
3
(5.7)
9
(5.7)
Sigmoid colon
17
(32.1)
56
(35.4)
Rectum
6
(11.3)
24
(15.2)
11
(20.8)
35
(22.2)
Presentation of PC
Primary tumor location
Neoadjuvant chemotherapy
0.905
0.831
Denominator differs if values are missing Bold values indicate that the difference between groups is significant PC peritoneal carcinomatosis, HIPEC hyperthermic intraperitoneal chemotherapy, BMI body mass index, SD standard deviation, ASA American Society of Anesthesiologists, ECOG Eastern Cooperative Oncology Group
morbidity after colorectal metastatic liver surgery as an important negative prognostic factor for the long-term outcome.19 These findings support the conclusion that postoperative complications, besides the obvious negative short-term consequences, strongly affect the long-term outcome for patients after colorectal surgery. Therefore, improving patient selection by identifying patients at risk for severe morbidity may improve both short- and longterm outcomes after CRS ? HIPEC.
The current study identified the patient’s surgical history, recent smoking history, physical performance status, and extent of cytoreduction as important prognostic factors for severe morbidity. Especially patients with three or four risk factors had a greater than 70 % chance for the development of severe postoperative complications. Because CRS ? HIPEC often is the only option for these patients, the expected harm and benefit of this procedure should be considered carefully, making patient selection a major challenge.
Risk Factors for Morbidity after HIPEC TABLE 2 Univariate analysis of intra/postoperatively identified characteristics of colorectal PC patients undergoing cytoreduction and HIPEC Variable
Severe morbidity (Clavien–Dindo C3) Yes (N = 53)
p value No (N = 158)
n
%
n
%
B50
14
(26.4)
36
(22.8)
[50 T stage
39
(73.6)
122
(77.2)
B3
26
(50.0)
73
(46.8)
4
26
(50.0)
83
(53.2)
0
14
(26.4)
48
(30.6)
1
18
(34.0)
43
(27.4)
2
21
(39.6)
66
(42.0)
9
(17.0)
19
(12.0)
Experience (no. of performed procedures) 0.591
0.689
N status
Liver metastases
0.645
0.357
PCI score Median [range] ? [IQR]
9 [3–23] ? [6.5–12.5]
7 [1–25] ? [4–11.3]
0.008
Mean ± SD
10.7 ± 5.7
8.3 ± 5.0
0.005
Tumor differentiation grade Good
6
(11.3)
13
(8.3)
Moderate
32
(60.4)
106
(67.5)
Poor Signet ring cell carcinoma
9 6
(17.0) (11.3)
30 8
(19.1) (5.1)
11
(20.8)
30
(19.0)
0.778
B2
24
(45.3)
89
(57.1)
0.137
[2
29
(54.7)
67
(42.9)
R1
48
(92.3)
149
(94.3)
R2a
4
(7.7)
9
(5.7)
Mucinous adenocarcinoma
0.354
PSDSS
Resection score 0.740
Visceral resections (median [range])
3 [0–6]
2 [0–8]
0.016
Peritoneal resections (median [range])
2 [0–6]
1 [0–6]
0.104
Total resections (median [range])
6 [0–11]
4 [0–12]
0.009
HIPEC agent Mitomycin C
43
(82.7)
141
(89.2)
Oxaliplatin
9
(17.3)
17
(10.8)
14 31
(26.4) (58.5)
47 87
(29.7) (55.1)
0.214
Amount of bowel anastomoses 0 1 [1
0.889
8
(15.1)
24
(15.2)
Enterostomy
29
(54.7)
78
(49.4)
Median operative time (min; median [range])
390 (130–501)
352 [167–720]
0.090
Median blood loss (ml; median [range])
1000 (100–6400)
700 [100–6600]
0.035
0.500
Denominator differs if values are missing Bold values indicate that the difference between groups is significant PC peritoneal carcinomatosis, HIPEC hyperthermic intraperitoneal chemotherapy, PCI peritoneal cancer index, PSDSS peritoneal surface disease severity score
G. A. Simkens et al. TABLE 3 Postoperative outcomes after cytoreduction and HIPEC according to number of risk factors Variable
No. of risk factors 0 [n = 19 (%)]
1 [n = 95 (%)]
2 [n = 75 (%)]
3/4 [n = 22 (%)]
Severe morbidity rate
5.3
14.7
29.3
72.7
Reoperation rate
5.3
8.4
18.7
45.5
15.8
11.6
18.7
42.9
Prolonged ICU stay ([2 days) 30-day/in-hospital mortality rate
0
1.1
1.3
4.5
Hospital stay [14 days
26.3
20.0
34.7
59.1
Readmission rate
10.5
10.5
9.5
28.6
HIPEC hyperthermic intraperitoneal chemotherapy, ICU intensive care unit
100 Severe morbidity rate Reoperation rate
80
Prolonged ICU stay >2 days Prolonged hospital stay >14 days
Risk (%)
Readmission rate
60
40
20
0 0 (n = 19)
1 (n = 95)
2 (n = 75)
3/4 (n = 22)
Number of risk factors
FIG. 1 Postoperative outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS ? HIPEC) according to number of risk factors
The current study identified extensive surgery preceding CRS ? HIPEC (PSS [1) as the most important risk factor for severe morbidity. For patients with pseudomyxoma peritoneı¨, extensive surgery before CRS ? HIPEC has been associated with more extensive PC and higher morbidity rates.20 However, in colorectal cancer, this association never has been described previously. Previous surgical trauma may cause additional dissemination and progression of peritoneal tumor cells, thereby increasing the extent of CRS ? HIPEC and the corresponding risk of severe morbidity. However, solid evidence for this theory is lacking, and it therefore is an interesting subject for further research. A recent history of smoking was strongly correlated with severe morbidity as well. This is in line with a recent review in which current smokers had a 30 % higher risk of major morbidity and mortality after all types of major colorectal surgery.21 The authors of this review therefore
advocated for smoking cessation before elective colorectal surgery. The positive effect of short-term smoking cessation before surgery is not evident, although positive effects seem to be present for a smoking cessation period of 4 weeks or more preoperatively.22 Therefore, smoking cessation before CRS ? HIPEC should be encouraged. A poor performance status (ECOG [1) was another important prognostic factor for severe morbidity shown in the current study. This is in line with several other studies that associate an impaired physical performance status with a poor postoperative outcome after CRS ? HIPEC.7–9,23 An impaired physical performance status has been associated with poor survival outcome and impaired palliative treatment efficiency in metastasized colorectal cancer, but little is known about the relation between this score and postoperative outcome in other major surgery.24,25 The relation between poor performance status and severe morbidity illustrates the impact of CRS ? HIPEC on a patient’s physical reserve, which also is reflected in the higher complication rate after CRS ? HIPEC among patients with skeletal muscle depletion.26 Nutritional status measured by body mass index (BMI) was not associated with severe complications in the current study. In addition to the aforementioned preoperative factors, an increased number of resections were associated with an increased risk of severe morbidity as well. This association also was present in the number of visceral resections specifically. The number of peritoneal resections did not seem to influence the risk of postoperative morbidity, implying that the impact of surgery is mainly determined by the number of visceral resections instead of peritoneal resections. Baratti et al.7 described similar findings in the largest prognostic study available, although contrasting results in a small cohort of colorectal PC patients have been found as well.27 Nevertheless, the association between the number of resections and postoperative morbidity emphasizes that the estimated extent of surgery should always be taken into consideration when CRS ? HIPEC is planned for a patient, especially if an extensive resection is
Risk Factors for Morbidity after HIPEC TABLE 4 Prediction model for severe morbidity in colorectal PC patients undergoing cytoreduction and HIPEC Variable
p value
Regression coefficient
Intercept
Odds ratio (95 % CI)
Regression coefficient after bootstrapping (n = 1000)
-2.499
-2.368
Prior surgical score [1
0.011
1.118
3.06 (1.29–7.28)
Positive recent history of smoking
0.001
1.289
3.63 (1.65–7.94)
1.221
ECOG performance status [1
0.010
0.991
2.70 (1.30–5.72)
0.939
1.060
PC peritoneal carcinomatosis, HIPEC hyperthermic intraperitoneal chemotherapy, ECOG Eastern Cooperative Oncology Group, CI confidence interval
Candidate for CRS + HIPEC
Smoking
Yes
No
PSS > 1
Risk (95% CI)
PSS > 1
No
Yes
No
Yes
ECOG > 1
ECOG > 1
ECOG > 1
ECOG > 1
No
Yes
No
Yes
No
Yes
No
Yes
9% (3% - 20%)
19% (8% - 40%)
24% (17% - 33%)
45% (27% - 64%)
21% (9% - 44%)
41% (20% - 66%)
48% (30% - 66%)
70% (48% - 86%)
FIG. 2 Risk of severe morbidity after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS ? HIPEC) according to major preoperative risk factors
expected for a patient with a high preoperative risk of severe morbidity. The PCI score is the preferred tool for estimating the extent of surgery at laparoscopy/laparotomy. Indeed, the PCI score was univariately associated with severe morbidity in the current study. However, this association did not remain statistically significant in the multivariate analysis, probably because the extent of surgery also was included in this analysis. To assess the risk of severe morbidity before surgery, a prediction model with preoperative risk factors was constructed and internally validated. The main purpose of this model was to create an intuitive and easy-to-use tool to assist in the decision making before CRS ? HIPEC. In the current cohort, this model gave an acceptable preoperative assessment of the risk for severe morbidity. Although internal validation was performed and showed little overoptimism, external validation would be a valuable subject of further research.
In the current study, comorbidities such as cardiovascular diseases and diabetes were not associated with postoperative complications, in contrast with two other studies.8,9 Because specific elements of the peritoneal surface disease severity score (PSDSS) such as the PCI score and the clinical symptoms of a patient might be of prognostic significance for short-term postoperative outcome, this study investigated the association between the PSDSS and severe morbidity. However, for the current cohort, there seemed to be no prognostic value in predicting postoperative severe complications. The use of neoadjuvant chemotherapy was not associated with an increased risk of severe morbidity. However, future research is needed to assess the specific impact of the type and timing of neoadjuvant treatment on the outcome after CRS ? HIPEC. The experience of the current HIPEC center (‘‘learning curve’’) did not seem to influence the severe morbidity rate. This may have resulted from the
G. A. Simkens et al.
introduction, training, and tutoring of the CRS ? HIPEC procedure by a strict protocol supervised by experts in this operation.28 The percentage of severe complications experienced by patients with oxaliplatin as the HIPEC agent seemed higher, but this difference was not statistically significant. In the current study, only a small number of patients were treated with oxaliplatin because systemic toxicity was observed in some of these patients. However, this cannot be objectified based on the current results and is not evidently supported by the literature.29 Surprisingly, an increased number of bowel anastomoses was not associated with severe morbidity, probably because the majority of patients with [1 anastomosis had at least one small bowel anastomosis. Small bowel anastomoses are known to be less vulnerable and to result less frequently in severe complications than large bowel anastomoses. Because the current study included a relatively small number of patients, the results in this study should be interpreted with caution. Furthermore, this analysis was conducted over several years, and more experience may have led to changes in patient selection, so a selection bias cannot be ruled out. Nevertheless, because the current study currently is the largest available investigation that included only colorectal patients, these results add valuable prognostic information to the sparse evidence on risk factors for severe morbidity experienced by patients with PC of a colorectal origin. CONCLUSIONS Extensive prior surgery, a recent smoking history, a poor performance status, and extensive cytoreduction are independent prognostic factors for severe morbidity in patients with colorectal PC undergoing CRS ? HIPEC. Especially patients with a combination of these risk factors have a substantial risk for severe morbidity and should be selected carefully for CRS ? HIPEC. The preoperative decision model can be a valuable tool in this process of patient selection. DISCLOSURE
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There are no conflicts of interest. 15.
REFERENCES 1. Elias D, Gilly F, Boutitie F, et al. Peritoneal colorectal carcinomatosis treated with surgery and perioperative intraperitoneal chemotherapy: retrospective analysis of 523 patients from a multicentric French study. J Clin Oncol. 2010;28:63–8. 2. Chua TC, Yan TD, Saxena A, Morris DL. Should the treatment of peritoneal carcinomatosis by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy still be regarded as a highly
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