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Annals of Surgical Oncology

, Volume 26, Issue 8, pp 2595–2604 | Cite as

RAS Mutation Decreases Overall Survival After Optimal Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy of Colorectal Peritoneal Metastasis: A Modification Proposal of the Peritoneal Surface Disease Severity Score

  • A. Arjona-SanchezEmail author
  • L. Rodriguez-Ortiz
  • D. Baratti
  • M. A. Schneider
  • A. Gutiérrez-Calvo
  • A. García-Fadrique
  • J. B. Tuynman
  • P. A. Cascales-Campos
  • V. Concepción Martín
  • R. Morales
  • G. I. Salti
  • X. Arteaga
  • D. Pacheco
  • J. Alonso-Gomez
  • O. Yalkin
  • P. Villarejo-Campos
  • J. M. Sanchez-Hidalgo
  • A. Casado-Adam
  • A. Cosano-Alvarez
  • S. Rufian-Peña
  • J. Briceño
Peritoneal Surface Malignancy

Abstract

Background

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are currently the most accepted treatment for peritoneal metastases from colorectal cancer. Restrictive selection criteria are essential to obtain the best survival benefits for this complex procedure. The most widespread score for patient selection, the peritoneal surface disease severity score (PSDSS), does not include current biological factors that are known to influence on prognosis. We investigated the impact of including RAS mutational status in the selection criteria for these patients.

Methods

We studied the risk factors for survival by multivariate analysis using a prospective database of consecutive patients with carcinomatosis from colorectal origin treated by CRS and HIPEC in our unit from 2009 to 2017. The risk factors obtained were validated in a multicentre, international cohort, including a total of 520 patients from 15 different reference units.

Results

A total of 77 patients were selected for local análisis. Only RAS mutational status (HR: 2.024; p = 0.045) and PSDSS stage (HR: 2.90; p = 0.009) were shown to be independent factors for overall survival. Early PSDSS stages I and II associated to RAS mutations impaired their overall survival with no significant differences with PSDSS stage III overall survival (p > 0.05). These results were supported by the international multicentre validation.

Conclusions

By including RAS mutational status, we propose an updated RAS-PSDSS score that outperforms PSDSS alone providing a quick and feasible preoperative assessment of the expected overall survival for patients with carcinomatosis from colorectal origin undergone to CRS + HIPEC.

Notes

Acknowledgment

The authors thank Dr. Jesus Esquivel for the diffusion of our study proposal to the different groups belonging to ASPSM (American Society Peritoneal Surface Malignancies). They also thank Dr. Pera (Department of Surgery of Hospital del Mar, Barcelona, Spain) for the review of the paper and Dr. Merlo (University Hospital Reina Sofia Cordoba, Spain) and Dra. Sluiter (Department of Surgery, VU. University Medical Center, Amsterdam, The Netherlands) for the collection of the data.

References

  1. 1.
    Mirnezami R, Mehta AM, Chandrakumaran K, et al. Cytoreductive surgery in combination with hyperthermic intraperitoneal chemotherapy improves survival in patients with colorectal peritoneal metastases compared with systemic chemotherapy alone. Br J Cancer. 2014;111:1500–8.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Arjona-Sánchez A, et al. Peritoneal metastases of colorectal origin treated by cytoreduction and HIPEC: an overview. World J Gastrointest Oncol. 2014;6:407.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Franko J, Ibrahim Z, Gusani NJ, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion versus systemic chemotherapy alone for colorectal peritoneal carcinomatosis. Cancer. 2010;116:3756–62.CrossRefGoogle Scholar
  4. 4.
    Cavaliere F, De Simone M, Virz S, et al. Prognostic factors and oncologic outcome in 146 patients with colorectal peritoneal carcinomatosis treated with cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy: Italian multicenter study S.I.T.I.L.O. Eur J Surg Oncol. 2011; 37: 148–54.Google Scholar
  5. 5.
    Kwakman R, Schrama AM, van Olmen JP, et al. Clinicopathological parameters in patient selection for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal cancer metastases: a meta-analysis. Ann Surg. 2016;263(6):1102–11.CrossRefPubMedGoogle Scholar
  6. 6.
    Pelz O, Stojadinovic A, Nissan A, Hohenberger W, Esquivel J. Evaluation of a peritoneal surface disease severity score in patients with colon cancer and peritoneal dissemination. J Surg Oncol. 2009;99:9–15.CrossRefPubMedGoogle Scholar
  7. 7.
    Esquivel J, Lowy AM, Markman M, et al. The American Society of peritoneal surface malignancies (ASPSM) multi-institution evaluation of the peritoneal surface disease severity score (PSDSS) in 1,013 patients with colorectal cancer with peritoneal carcinomatosis. Ann Surg Oncol. 2014;21:4195.CrossRefGoogle Scholar
  8. 8.
    Vauthey JN, Zimmitti G, Kopetz SE, et al. RAS mutations status predicts survival and patterns of recurrence in patients undergoing hepatectomy for colorectal liver metastases. Ann Surg. 2013;258:619–26.CrossRefPubMedGoogle Scholar
  9. 9.
    Karapetis CS, Khambata-Ford S, Jonker DJ, et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 2008;359:1757–65.CrossRefGoogle Scholar
  10. 10.
    De Roock W, Claes B, Bernasconi D, et al. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy–refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol. 2010;11:753–62.CrossRefPubMedGoogle Scholar
  11. 11.
    Arjona-Sanchez A, Cadenas-Febres A, Cabrera-Bermon J, et al. Assessment of RIFLE and AKIN criteria to define acute renal dysfunction for HIPEC procedures for ovarian and nonovarian peritoneal malignances. Eur J Surg Oncol. 2016;42:869–76.CrossRefPubMedGoogle Scholar
  12. 12.
    COMPASS. Simkens GA, van Oudheusden TR, Nieboer D, et al. Development of a prognostic nomogram for patients with peritoneally metastasized colorectal cancer treated with cytoreductive surgery and HIPEC. Ann Surg Oncol. 2016;23:4214–21.Google Scholar
  13. 13.
    Demey K, Wolthuis A, de Buck van Overstraeten A, et al. External validation of the prognostic nomogram (COMPASS) for patients with peritoneal carcinomatosis of colorectal cancer. Ann Surg Oncol 2017.  https://doi.org/10.1245/s10434-017-6042-9.CrossRefPubMedGoogle Scholar
  14. 14.
    Cashin PH, Graf W, Nygren P, Mahteme H. Patient selection for cytoreductive surgery in colorectal peritoneal carcinomatosis using serum tumor markers: an observational cohort study. Ann Surg. 2012;256:1078–83.CrossRefPubMedGoogle Scholar
  15. 15.
    Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26:1626–34.CrossRefGoogle Scholar
  16. 16.
    Douillard J-Y, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, et al. Panitumumab–FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med. 2013;369:1023–34.CrossRefPubMedGoogle Scholar
  17. 17.
    Van Cutsem E, Kohne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009;360:1408–17.CrossRefGoogle Scholar
  18. 18.
    Lievre A, Bachet JB, Le Corre D, Boige V, Landi B, Emile JF, et al. KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res. 2006;66:3992–5.CrossRefPubMedGoogle Scholar
  19. 19.
    Brudvik KW, Kopetz SE, Li L, et al. Meta-analysis of KRAS mutations and survival after resection of colorectal liver metástasis. Br J Surg. 2015;102:1175–83.CrossRefPubMedGoogle Scholar
  20. 20.
    Brudvik KW, Jones PR, Giuliante F, et al. RAS mutation clinical risk score to predict survival after resection of colorectal liver metastasis. Ann Surg. 2017.  https://doi.org/10.1097/sla.0000000000002319.CrossRefGoogle Scholar
  21. 21.
    Prada-Villaverde A, Esquivel J, Lowy AM, et al. The American Society of peritoneal surface malignancies evaluation of HIPEC with mitomycin C versus oxaliplatin in 539 patients with colon cancer undergoing a complete cytoreductive surgery. J Surg Oncol. 2014.  https://doi.org/10.1002/jso.23728.
  22. 22.
    Hompes D, D’Hoore A, Wolthuis A, Fieuws S, Mirck B, Bruin S, et al. The use of Oxaliplatin or Mitomycin C in HIPEC treatment for peritoneal carcinomatosis from colorectal cancer: a comparative study. J Surg Oncol. 2014;109:527–32.CrossRefPubMedGoogle Scholar
  23. 23.
    Venderbosch S, Nagtegaal ID, Maughan TS, et al. Mismatch repair status and BRAF mutation status in metastatic colorectal cancer patients: a pooled analysis of the CAIRO, CAIRO2, COIN, and FOCUS studies. Clin Cancer Res. 2014;20:5322–30.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Society of Surgical Oncology 2019

Authors and Affiliations

  • A. Arjona-Sanchez
    • 1
    • 2
    Email author
  • L. Rodriguez-Ortiz
    • 1
  • D. Baratti
    • 3
  • M. A. Schneider
    • 4
  • A. Gutiérrez-Calvo
    • 5
  • A. García-Fadrique
    • 6
  • J. B. Tuynman
    • 7
  • P. A. Cascales-Campos
    • 8
  • V. Concepción Martín
    • 9
  • R. Morales
    • 10
  • G. I. Salti
    • 11
  • X. Arteaga
    • 12
  • D. Pacheco
    • 13
  • J. Alonso-Gomez
    • 14
  • O. Yalkin
    • 15
  • P. Villarejo-Campos
    • 16
  • J. M. Sanchez-Hidalgo
    • 1
    • 2
  • A. Casado-Adam
    • 1
    • 2
  • A. Cosano-Alvarez
    • 1
  • S. Rufian-Peña
    • 1
    • 2
  • J. Briceño
    • 1
    • 2
  1. 1.Oncologic and Pancreatic Surgery UnitUniversity Hospital Reina SofıaCórdobaSpain
  2. 2.Maimonides Biomedical Research Institute of Cordoba (IMIBIC), University of CordobaUniversity Hospital Reina SofıaCórdobaSpain
  3. 3.Peritoneal Surface Malignancy Program, Department of SurgeryFondazione IRCCS Instituto Nazionale TumoriMilanItaly
  4. 4.Department of Surgery and TransplantationUniversity Hospital of ZurichZurichSwitzerland
  5. 5.Surgery Department, Unit of Peritoneal Oncologic SurgeryHospital Príncipe de AsturiasAlcalá de Henares, MadridSpain
  6. 6.Department of SurgeryInstituto Valenciano de OncologíaValenciaSpain
  7. 7.Department of Medical OncologyVU University Medical CenterAmsterdamThe Netherlands
  8. 8.Departamento De Cirugía General, Unidad De Cirugía De La Carcinomatosis PeritonealVirgen De La Arrixaca University HospitalMurciaSpain
  9. 9.Unit of Peritoneal Oncologic Surgery and Colorectal SurgeryHospital University Nuestra Señora de la CandelariaTenerifeSpain
  10. 10.Unit of Oncologic and Pancreatic SurgeryHospital Son SpacesPalma de MallorcaSpain
  11. 11.Division of Surgical OncologyThe University of Illinois at Chicago Hospital and Health Sciences SystemChicagoUSA
  12. 12.Department of SurgeryDonostia HospitalSan SebastiánSpain
  13. 13.Gastroenterology Service, Liver Transplantation UnitRio Hortega HospitalValladolidSpain
  14. 14.Department of SurgeryH.U. Gran Canaria Dr. NegrínCanariasSpain
  15. 15.Department of Surgical OncologyAnkara University Faculty of MedicineAnkaraTurkey
  16. 16.Department of Surgical OncologyUniversity Hospital Ciudad RealCiudad RealSpain

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