SEARCH

SEARCH BY CITATION

Keywords:

  • colon;
  • rectal;
  • cancer;
  • peritoneal;
  • mitomycin

Abstract

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES

BACKGROUND:

Survival benefit of cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion was demonstrated by a prospective randomized trial for colorectal peritoneal carcinomatosis. Because of a recent substantial improvement in chemotherapy, the authors analyzed treatment options of colorectal carcinomatosis in the current era.

METHODS:

Consecutive patients with colorectal carcinomatosis treated by cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion from 2001 to 2007 were included. The control group patients with carcinomatosis received contemporary chemotherapy alone. Overall survival was the primary endpoint.

RESULTS:

All patients underwent systemic chemotherapy. The cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion group (n = 67) was similar to the control group (n = 38) in sex, tumor grade, site of tumor origin, T status, and N status. The control group was, however, older (59 vs 51 years; P<.001). Median survival measured from the diagnosis of peritoneal disease was longer with cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion (34.7 months vs 16.8 months; P<.001). Presence of liver metastasis was a significant negative predictor of survival (hazard ratio, 2.13).

CONCLUSIONS:

The authors concluded that 1) contemporary chemotherapy is associated with prolonged survival among patients with carcinomatosis as compared with historical controls, and 2) addition of cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion to modern chemotherapy regimens may significantly prolong survival. Cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion and systemic chemotherapy are not competitive therapies, and they both have a role in a multidisciplinary approach to patients with carcinomatosis. Cancer 2010. © 2010 American Cancer Society.

Peritoneal carcinomatosis from colorectal cancer has been historically associated with poor survival ranging from 5 to 7 months, and few therapeutic or palliative options.1-4 These patients more than many other cancer patients suffer from significant and disabling symptoms as a direct result of local tumor progression. As a result, development in this field has largely focused on innovative surgical approaches in an attempt to control or palliate the locoregional progression in the absence of systemic extraperitoneal disease. Multiple institutional5-9 and multi-institutional series10, 11 have suggested improved survival with cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion. Nevertheless, these were cohort studies with no internal controls; comparison was made to historical controls.

To our knowledge, there are only 2 published studies on cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion for colorectal carcinomatosis with internal controls: a Dutch prospective randomized trial12 and a French case-control retrospective study.13 In the former, significantly prolonged median survival was observed in the group receiving cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion and systemic chemotherapy (12.6 vs 22.3 months; P = .032), as compared with the best systemic chemotherapy alone.12, 14 Given the standard of care during the enrollment period, however, a majority of the patients in this randomized trial received only 5-fluorouracil as the best systemic chemotherapy option. A more recent French retrospective multi-institutional study demonstrated median survival of 23.9 months in the standard group versus 62.7 months in the hyperthermic intraperitoneal chemoperfusion group (P<.05).13

Although there are several cohort reports on cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion for colorectal carcinomatosis from US institutions,8, 9, 15 no comparative study with internal controls has yet been published. In addition, available data on treatment of peritoneal carcinomatosis did not result in widespread acceptance, despite endorsement from field leaders16 and a recent favorable meta-analysis.17 Another prospective randomized trial may put this issue to rest. Given patient preferences, however, it is likely that any future trial will fail to accrue, as evidenced previously.5 Hence, we believe it is important to report high-volume institutional results until another prospective trial is conducted.

Therefore, we set out to evaluate the contribution of cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion to survival in patients with carcinomatosis in the modern chemotherapy era. We compared our experience with cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion for colorectal carcinomatosis against a contemporary cohort of patients receiving systemic therapy but no cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion at our institution.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES

We analyzed 105 patients with peritoneal carcinomatosis of colorectal origin diagnosed between 2001 and 2007. The primary outcome measure was survival measured from the diagnosis of peritoneal carcinomatosis. This study received approval from the University of Pittsburgh Institutional Review Board. Cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion was performed at 2 closely related institutions by the same physician team. The unique setup of the University of Pittsburgh Medical Center Cancer Centers Network connects the main institution with >40 network community sites covering a geographic area of >200 miles around greater Pittsburgh. The centralized registry allows analysis of all patients treated within this large network. Therefore, we were able to construct a control group with confirmed carcinomatosis from patients who either refused cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion treatment or referral, or were never referred because of logistic or geographical issues.

Patient Selection and Data Collection

Sixty-seven consecutive patients underwent cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion procedure and systemic chemotherapy for metastatic colorectal cancer. The control group was selected by a review of the institutional multihospital cancer registry and consisted of 38 patients. Control group inclusion criteria were 1) asymptomatic peritoneal carcinomatosis of colorectal origin; 2) aggressive systemic chemotherapy; and 3) primary tumor removed, but did not undergo cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion. Control group exclusion criteria included 1) poor performance status, 2) intent for supportive care only, and 3) unresectable carcinomatosis volume as judged by computed tomography (CT) scan review. The diagnosis of peritoneal carcinomatosis in the control group was verified by a surgical procedure or by the development of obvious evidence of carcinomatosis on CT scan. Presence of limited liver involvement (superficial lesions only) was allowed in both groups. Demographics, tumor characteristics (grade, TNM stage, and site of original tumor), chemotherapy treatment, and survival outcome were analyzed.

Surgical Approach

Our standard operative approach is described in detail elsewhere.7 Briefly, a midline laparotomy was followed by complete adhesiolysis, omentectomy, and selective peritonectomy in all patients. Cytoreductive surgery with resection of tumor masses and/or organs then followed, with the objective of rendering patients with no visible disease. Hyperthermic chemoperfusion was achieved using a closed abdomen perfusion technique with 3 L of perfusate containing 30 mg mitomycin C for the first hour followed by an additional 10 mg for 40 more minutes using a roller-pump heat exchanger perfusion machine (ThermoChem HT-1000, ThermaSolutions, Melbourne, Fla). This was followed by a reconstruction phase and laparotomy closure.

Statistical Analysis

To examine baseline differences in the data, a t test and chi-square tests were performed. The 2-sample Student t test was used to determine whether there was a significant relationship between age and group (control vs cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion). Chi-square tests were used to determine whether there were any significant relationships between group and the following categorical variables: sex, tumor grade (grade I/II vs grade III), site of origin (colon vs rectum), liver lesion (absent vs present), and prior treatment with oxaliplatin, irinotecan, and biological agents.

Survival was measured from the date of diagnosis of peritoneal disease to the date of last follow-up or death and was estimated using the Kaplan-Meier method. Log-rank tests were performed to examine the univariate associations between survival and clinical variables. Cox proportional hazard models were built using all variables with P <.2 in univariate testing. Other variables that were felt to be important10, 18 predictors of survival were also investigated, such as chemotherapy agents, tumor grade, and metastatic versus nonmetastatic status at presentation. Because tumor grade violated the proportional hazard assumption, both grade-stratified and unstratified models without tumor grade were created. Statistical significance was assumed at .05.

RESULTS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES

There was no statistical difference between the groups in distribution of sex, tumor grade, site of origin (colon vs rectum), and T and N classification of the original tumor. However, the control group was older (mean 59 years in the control group vs mean 51 years in the hyperthermic intraperitoneal chemoperfusion group; P<.001), had a higher proportion of patients who were diagnosed with carcinomatosis at their initial presentation (76% vs 42%; P<.001), and had a higher proportion of patients with liver lesion (35% vs 15%; P = .014).

All patients received systemic chemotherapy. There were no differences between the 2 groups in administration of 5-fluorouracil and irinotecan, but the control group was less likely to receive oxaliplatin (47% vs 78%; P = .001) and biological agents (bevacizumab and/or cetuximab, 18% vs 59%; P<.0001). Six patients in the cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion group received a suboptimal debulking (R2), but remained included in the study.

Median survival measured from the diagnosis of peritoneal disease was longer with cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion (34.7 months vs 16.8 months; P<.001; Fig. 1). Besides cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion, only chemotherapy with biological agents and absence of liver metastasis were associated with survival advantage in the univariate testing (Table 1). Sex, tumor grade, site of primary tumor origin (colonic vs rectal), and presence of carcinomatosis at initial cancer diagnosis (stage I-III vs stage IV/carcinomatosis) were not associated with survival.

thumbnail image

Figure 1. Kaplan-Meier estimator curves comparing the group treated with cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion (CS-HIPEC) versus the control group are shown. Chemo indicates chemotherapy.

Download figure to PowerPoint

Table 1. Univariate Survival Analysis
CharacteristicsMedian Survival, moStatistical Significancea
  • CS-HIPEC indicates cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion.

  • a

    Factors found to be associated with survival were CS-HIPEC, the presence of a liver lesion, and systemic chemotherapy with a biologic agent.

Group  
 Control16.8<.001
 CS-HIPEC34.7 
Sex  
 Women26.3.777
 Men26.2 
Grade  
 1 and 227.5.322
 317.8 
Site of origin  
 Colon26.9.109
 Rectum16.8 
Initial presentation  
 Primary tumor with carcinomatosis26.3.825
 Stage I-III primary tumor26.3 
Liver lesion  
 Absent30.3.001
 Present16.5 
Oxaliplatin  
 No26.3.323
 Yes26.3 
Irinotecan  
 No27.5.946
 Yes26.3 
Biological agent  
 No19.7.020
 Yes30.3 

Multivariate Cox proportional hazards modeling was performed on all patients with available data. Tumor grade was the only variable that violated the proportional hazard assumption. On detailed analysis, there is some evidence that tumor grade affects survival, particularly at early times. Conversely, tumor grade is not a confounder, because it is not associated with cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion treatment.

Therefore, 3 Cox proportional hazard regression models were developed, where the latter 2 represent sensitivity analysis and point to the robustness of the results. There were 91 cases available for the first model, which included significant predictor variables from univariate testing (Table 2). Tumor grade lacked the predefined entry P value and consequently was not included in this model. Delivery of cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion was a significant predictor of survival after adjusting for all other variables. Presence of liver metastasis was a negative significant predictor of survival, and its effect size was comparable to that of cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion. Carcinomatosis from rectal primary tumors portends a substantially worse prognosis than that from a colon primary tumor. Age and the presence of carcinomatosis at initial presentation of cancer were not predictive of survival. Moreover, chemotherapy with oxaliplatin or a biological agent was also not a predictor of survival.

Table 2. Multivariate Cox Regression Model for Survival Since Diagnosis of Carcinomatosis Adjusted for Baseline Predictorsa
ParameterStatistical SignificanceHR95% HR CI
  • HR indicates hazard ratio; CI, confidence limits.

  • a

    A total of 91 cases were available for analysis; overall P = .002.

  • b

    Group: group treated with systemic chemotherapy alone as the referent versus the group treated with cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion (CS-HIPEC). The risk of death was found to be significantly lowered among patients treated with CS-HIPEC (HR, 0.421). A HR >1 indicates an increased risk of death.

Group (referent: control)b.02730.4210.195-0.907
Site of origin (referent: colon).05882.2370.971-5.154
Liver lesion.03662.1331.049-4.341
Biological agents.46720.7760.392-1.536
Oxaliplatin.86240.9450.496-1.798
Age.58251.0080.981-1.035
Carcinomatosis at initial presentation.13790.6070.314-1.174

We attempted to include tumor grade as a variable in the analysis. Because tumor grade did not follow the proportional hazard assumption, the second model was stratified on tumor grade. There were 75 cases with data available for this analysis: 51 patients in stratum 1 (grade I-II) and 24 patients in stratum 2 (grade III, Fig. 2). Each group has a distinct baseline hazard function, but common values for the coefficients.19 The relative effect of each predictor is assumed the same across strata. The presence of liver lesion(s) was the only significant predictor of survival in the model (Table 3).

thumbnail image

Figure 2. Schematic diagram of the number of patients in each group is shown stratified by grade. This drawing represents patients with complete data used by Cox models. HIPEC indicates hyperthermic intraperitoneal chemoperfusion.

Download figure to PowerPoint

Table 3. Multivariate Cox Regression Model Stratified Based on Tumor Gradea
ParameterStatistical SignificanceHR95% HR CI
  • HR indicates hazard ratio; CI, confidence limits.

  • a

    A total of 75 cases were available for analysis; overall P=.002.

  • b

    Group: group treated with systemic chemotherapy alone as referent versus group treated with cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion (CS-HIPEC). The risk of death was not found to be significantly altered among patients treated with CS-HIPEC (P=.242).

Group (referent: control)b.24260.5980.253-1.416
Site of origin (referent: colon).13942.2470.768-6.572
Liver lesion.00303.5751.540-8.298
Biological agents.16200.5920.284-1.235
Oxaliplatin.95021.0220.512-2.041
Age.59621.0090.977-1.041
Carcinomatosis at initial presentation.29400.6870.341-1.385

To further investigate the effect of missing values for tumor grade, we developed a third model. This model included 91 cases, and contained all variables from the first model plus a dummy variable for whether grade was reported. There was no substantial change of covariate values, and the regression coefficient for the dummy variable was not statistically significant (data not shown).

DISCUSSION

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES

Great progress in treatment of metastatic colorectal cancer has been noted since the turn of the millennium, with median survival exceeding 20 months. Nevertheless, cure with chemotherapy remains rare, and prospectively observed 5-year survival in participants of trials is 1.1%.20 Colorectal carcinomatosis has been associated with particularly poor prognosis, with median survival traditionally reported to be around 6 months.1-4

Cytoreductive surgery and intraperitoneal chemotherapy have been successfully used in ovarian cancer and are increasing reported in colorectal carcinomatosis. Many authors have reported encouraging survival of patients with peritoneal carcinomatosis from colorectal cancer treated with cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion.7-11, 21, 22 However, these studies compared cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion to historical controls, and some were performed before the widespread availability of modern chemotherapy regimens. Similarly, in the only randomized trial demonstrating an advantage to cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion, 5-fluorouracil alone was the dominant chemotherapy regimen. Introduction of irinotecan, oxaliplatin, and bevacizumab has been well documented to lead to improvement of median survival among those with previously untreated metastatic colorectal cancer and good performance status.23, 24 It remains undefined whether these improvements can be extrapolated to patients with peritoneal carcinomatosis. Nonetheless, it is reasonable to assume a positive effect of present-day chemotherapy on peritoneal carcinomatosis. Indeed, in this contemporary series we observed a median survival of 16.8 months among those in the control group, with peritoneal carcinomatosis from colorectal cancer treated by best systemic chemotherapy alone. This represents a substantial improvement as compared with traditionally cited historical controls.1-4, 12 Longer median survival of 23.9 months has been recently reported among French patients with asymptomatic colorectal carcinomatosis treated with modern chemotherapy alone.13 Our data support that 1) contemporary chemotherapy is associated with prolonged survival among patients with carcinomatosis as compared with historical controls, and 2) addition of cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion to modern chemotherapy regimens significantly prolongs survival in selected patients.

Beyond the Dutch prospective randomized trial and the current report, there is only 1 additional study of cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion in colorectal carcinomatosis with internal controls. Elias et al examined patients with asymptomatic colorectal carcinomatosis treated by modern chemotherapy versus those treated by cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion.13 The cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion cohort received oxaliplatin 460 mg/m2 30-minute hyperthermic intraperitoneal chemoperfusion after cytoreduction and survived significantly longer (62.7 vs 23.9 months; P<.05). Our protocol uses traditional mitomycin C (40 mg total dose over 100-minute perfusion) and resulted in comparatively shorter survival of 34.7 months. Although these 2 studies cannot be directly compared, oxaliplatin may be superior to traditional mitomycin C for intraperitoneal application. Nevertheless, both the French13 and our study support superiority of cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion therapy for a select population of patients with peritoneal colorectal carcinomatosis as previously demonstrated by the randomized trial.12, 14 In the context of survival analysis, it is necessary to point out major methodological differences in calculating survival times; comparative retrospective studies, such as the study of Elias et al13 and the present study, calculate survival from the diagnosis of peritoneal carcinomatosis. In contrast, single-arm observational studies8, 10 calculate survival from the cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion procedure, whereas the randomized trial measured survival since randomization.12, 14

We recognize several inherent limitations to this type of study and have attempted to limit bias in the analysis. First, we excluded patients with poor performance status and supportive care only. We required presence of initially asymptomatic carcinomatosis and at least 4 cycles of chemotherapy for inclusion in the control arm. Because performance status affects survival, this approach limits selection bias toward poor-performance patients entering the control group. Second, to avoid lead-in bias, we elected to report survival measured from diagnosis of peritoneal carcinomatosis for the purpose of comparison between the groups. Because selection of control group in retrospective studies always has to be presumed as biased, we took special precautions to limit the selection bias. This resulted in a relatively limited number of control cases. Similarly, Elias et al13 collected a limited number of their control cases among 5 large cancer centers. The unique setup of our institution (a network of cancer centers) permits for analysis of data from many cancer centers and allowed us to construct our control group in a similar fashion to that of Elias et al.13

We investigated the prognostic value of certain predictors. The prognostic usefulness of tumor grade in colorectal carcinomatosis is poorly elucidated, and remains controversial. In agreement with others,18 the survival difference by tumor grade was not significant in this study. On the contrary, worsening prognosis was associated with a higher tumor grade in pooled analysis.10 Baseline hazard functions for tumor grade were not proportional in this cohort. Therefore, the effect of tumor grade on survival was difficult to evaluate in multivariate models. Hopefully, future studies will explain the interaction of tumor grade, other clinical variables, and role of cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion in the treatment of peritoneal carcinomatosis from colorectal cancer. It is also interesting that rectal origin of carcinomatosis had a highly negative impact on survival in 1 of our multivariate models. Although Verwaal et al observed 5.6 months shorter median survival among patients with a rectal primary tumor, their observation did not reach statistical significance.12 Similarly, others reported no survival difference between rectal and colonic origin of peritoneal carcinomatosis.10 Lastly, we chose to allow the presence of concurrent liver metastases in both of our cohorts. Negative prognostic effect of liver lesion has been observed in this study and by others,10, 11 but contrary reports are equally available.4, 25

A multidisciplinary approach to metastatic colorectal cancer is rapidly evolving. Surgical treatment of hepatic26, 27 and/or pulmonary28 metastases is considered appropriate in selected patients. It remains interesting that although no prospective randomized trial has ever been conducted to evaluate the efficacy of liver resection for colorectal liver metastases, this therapy is recognized worldwide as a standard of care for colorectal liver metastases. Direct retrospective comparison of cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion and liver resection for colorectal liver metastases suggests that both bring a similar magnitude of survival benefit29, 30 to selected patients with stage IV disease.

Cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion may be associated with survival benefit in selected patients with peritoneal carcinomatosis from colorectal cancer. This benefit appears to be preserved even among patients with modern chemotherapy. It is important to note that cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion and systemic chemotherapy are not competitive therapies, but rather complementary techniques. This analysis supports that cytoreductive surgery combined with hyperthermic intraperitoneal perfusion has a role in the multidisciplinary approach to patients suffering from colorectal carcinomatosis.

Acknowledgements

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES

We thank A. Schneider and S. Winters for their assistance with cancer registry data.

REFERENCES

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES
  • 1
    Chu DZ, Lang NP, Thompson C, Osteen PK, Westbrook KC. Peritoneal carcinomatosis in nongynecologic malignancy. A prospective study of prognostic factors. Cancer. 1989; 63: 364-367.
  • 2
    Jayne DG, Fook S, Loi C, Seow-Choen F. Peritoneal carcinomatosis from colorectal cancer. Br J Surg. 2002; 89: 1545-1550.
  • 3
    Koppe MJ, Boerman OC, Oyen WJ, Bleichrodt RP. Peritoneal carcinomatosis of colorectal origin: incidence and current treatment strategies. Ann Surg. 2006; 243: 212-222.
  • 4
    Sadeghi B, Arvieux C, Glehen O, et al. Peritoneal carcinomatosis from non-gynecologic malignancies: results of the EVOCAPE 1 multicentric prospective study. Cancer. 2000; 88: 358-363.
  • 5
    Elias D, Delperro JR, Sideris L, et al. Treatment of peritoneal carcinomatosis from colorectal cancer: impact of complete cytoreductive surgery and difficulties in conducting randomized trials. Ann Surg Oncol. 2004; 11: 518-521.
  • 6
    Elias D, Goere D, Blot F, et al. Optimization of hyperthermic intraperitoneal chemotherapy with oxaliplatin plus irinotecan at 43 degrees C after compete cytoreductive surgery: mortality and morbidity in 106 consecutive patients. Ann Surg Oncol. 2007; 14: 1818-1824.
  • 7
    Gusani NJ, Cho SW, Colovos C, et al. Aggressive surgical management of peritoneal carcinomatosis with low mortality in a high-volume tertiary cancer center. Ann Surg Oncol. 2008; 15: 754-763.
  • 8
    Sugarbaker PH, Jablonski KA. Prognostic features of 51 colorectal and 130 appendiceal cancer patients with peritoneal carcinomatosis treated by cytoreductive surgery and intraperitoneal chemotherapy. Ann Surg. 1995; 221: 124-132.
  • 9
    Shen P, Hawksworth J, Lovato J, et al. Cytoreductive surgery and intraperitoneal hyperthermic chemotherapy with mitomycin C for peritoneal carcinomatosis from nonappendiceal colorectal carcinoma. Ann Surg Oncol. 2004; 11: 178-186.
  • 10
    Glehen O, Kwiatkowski F, Sugarbaker PH, et al. Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study. J Clin Oncol. 2004; 22: 3284-3292.
  • 11
    Cavaliere F, Perri P, Rossi CR, et al. Sitilo experience on peritoneal carcinomatosis from colorectal cancer: clinical prognostic features. J Exp Clin Cancer Res. 2003; 22( 4 suppl): 29-33.
  • 12
    Verwaal VJ, van Ruth S, de Bree E, et al. Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol. 2003; 21: 3737-3743.
  • 13
    Elias D, Lefevre JH, Chevalier J, et al. Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin. J Clin Oncol. 2009; 27: 681-685.
  • 14
    Verwaal VJ, Bruin S, Boot H, van Slooten G, van Tinteren H. 8-Year follow-up of randomized trial: cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy in patients with peritoneal carcinomatosis of colorectal cancer. Ann Surg Oncol. 2008; 15: 2426-2432.
  • 15
    McQuellon RP, Loggie BW, Lehman AB, et al. Long-term survivorship and quality of life after cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy for peritoneal carcinomatosis. Ann Surg Oncol. 2003; 10: 155-162.
  • 16
    Esquivel J, Sticca R, Sugarbaker P, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal surface malignancies of colonic origin: a consensus statement. Society of Surgical Oncology. Ann Surg Oncol. 2007; 14: 128-133.
  • 17
    Cao C, Yan TD, Black D, Morris DL. A systematic review and meta-analysis of cytoreductive surgery with perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis of colorectal origin. Ann Surg Oncol. 2009; 16: 2152-2165.
  • 18
    Carmignani CP, Ortega-Perez G, Sugarbaker PH. The management of synchronous peritoneal carcinomatosis and hematogenous metastasis from colorectal cancer. Eur J Surg Oncol. 2004; 30: 391-398.
  • 19
    Therneau T, Grambsch P. Modeling Survival Data: Extending the Cox Model. New York, NY: Springer-Verlag; 2000.
  • 20
    Dy GK, Hobday TJ, Nelson G, et al. Long-term survivors of metastatic colorectal cancer treated with systemic chemotherapy alone: a north central cancer treatment group review of 3811 patients, n0144. Clin Colorectal Cancer. 2009; 8: 88-93.
  • 21
    Culliford AT, Brooks AD, Sharma S, et al. Surgical debulking and intraperitoneal chemotherapy for established peritoneal metastases from colon and appendix cancer. Ann Surg Oncol. 2001; 8: 787-795.
  • 22
    Elias D, Raynard B, Farkhondeh F, et al. Peritoneal carcinomatosis of colorectal origin. Gastroenterol Clin Biol. 2006; 30: 1200-1204.
  • 23
    Goldberg RM, Sargent DJ, Morton RF, et al. A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol. 2004; 22: 23-30.
  • 24
    Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004; 350: 2335-2342.
  • 25
    Kianmanesh R, Scaringi S, Sabate JM, et al. Iterative cytoreductive surgery associated with hyperthermic intraperitoneal chemotherapy for treatment of peritoneal carcinomatosis of colorectal origin with or without liver metastases. Ann Surg. 2007; 245: 597-603.
  • 26
    Nordlinger B, Guiguet M, Vaillant JC, et al. Surgical resection of colorectal carcinoma metastases to the liver. A prognostic scoring system to improve case selection, based on 1568 patients. Association Francaise de Chirurgie. Cancer. 1996; 77: 1254-1262.
  • 27
    Nordlinger B, Sorbye H, Glimelius B, et al. Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. Lancet. 2008; 371: 1007-1016.
  • 28
    Miller G, Biernacki P, Kemeny NE, et al. Outcomes after resection of synchronous or metachronous hepatic and pulmonary colorectal metastases. J Am Coll Surg. 2007; 205: 231-238.
  • 29
    Franko J, Gusani NJ, Holtzman MP, Ahrendt SA, Zeh HJ III, Bartlett DL. Case-matched comparison of survival after cytoreductive surgery and intraperitoneal hyperthermic chemoperfusion for peritoneal carcinomatosis versus liver resection for metastatic colorectal cancer [abstract]. J Clin Oncol. 2008; 26( 15 suppl): 4058.
  • 30
    Shen P, Thai K, Stewart JH, et al. Peritoneal surface disease from colorectal cancer: comparison with the hepatic metastases surgical paradigm in optimally resected patients. Ann Surg Oncol. 2008; 15: 3422-3432.