Skip to main content

Advertisement

SpringerLink
Log in

Preoperative Risk Score for Predicting Incomplete Cytoreduction: A 12-Institution Study from the US HIPEC Collaborative

  • Peritoneal Surface Malignancy
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

For patients with peritoneal carcinomatosis undergoing cytoreductive surgery with heated intraperitoneal chemotherapy (CRS/HIPEC), incomplete cytoreduction (CCR2/3) confers morbidity without survival benefit. The aim of this study is to identify preoperative factors which predict CCR2/3.

Methods

All patients who underwent curative-intent CRS/HIPEC of low/high-grade appendiceal, colorectal, or peritoneal mesothelioma cancers in the 12-institution US HIPEC Collaborative from 2000 to 2017 were included (n = 2027). The primary aim is to create an incomplete-cytoreduction risk score (ICRS) to predict CCR2/3 CRS utilizing preoperative data. ICRS was created from a randomly selected cohort of 50% of patients (derivation cohort) and verified on the remaining patients (validation cohort).

Results

Within our derivation cohort (n = 998), histology was low-grade appendiceal neoplasms in 30%, high-grade appendiceal tumor in 41%, colorectal tumor in 22%, and peritoneal mesothelioma in 8%. CCR0/1 was achieved in 816 patients and CCR 2/3 in 116 patients. On multivariable analysis, preoperative factors associated with incomplete cytoreduction were male gender [odds ratio (OR) 3.4, p = 0.007], presence of ascites (OR 2.8, p = 0.028), cancer antigen (CA)-125 ≥ 40 U/mL (OR 3.4, p = 0.012), and carcinoembryonic antigen (CEA) ≥ 4.2 ng/mL (OR 3.2, p = 0.029). Each preoperative factor was assigned a score of 0 or 1 to form an ICRS from 0 to 4. Scores were grouped as zero (0), low (1–2), or high (3–4). Incidence of CCR2/3 progressively increased by risk group from 1.6% in zero to 13% in low and 39% in high. When ICRS was applied to the validation cohort (n = 1029), this relationship was maintained.

Conclusion

The incomplete cytoreduction risk score incorporates preoperative factors to accurately stratify the risk of CCR2/3 resection in CRS/HIPEC. This score should not be used in isolation, however, to exclude patients from surgery.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Notes

  1. Emory University, The Ohio State University, University of California San Diego, University of Cincinnati, City of Hope National Medical Center, Johns Hopkins University, University of Massachusetts, Mayo Clinic, Medical College of Wisconsin, Moffitt Cancer Center, University of Texas MD Anderson Cancer Center, and University of Wisconsin.

References

  1. Glehen O, Mithieux F, Osinsky D, Beaujard AC, Freyer G, Guertsch PH, et al. Surgery combined with peritonectomy procedures and intraperitoneal chemohyperthermia in abdominal cancers with peritoneal carcinomatosis: a phase II study. J Clin Oncol. 2003;21(5):799–806.

    Article  CAS  Google Scholar 

  2. Morano WF, Khalili M, Chi DS, Bowne WB, Esquivel J. Clinical studies in CRS and HIPEC: Trials, tribulations, and future directions-A systematic review. J Surg Oncol. 2018;117(2):245–9.

    Article  Google Scholar 

  3. Sugarbaker PH, Peritoneal metastases, a frontier for progress. Surg Oncol Clin N Am. 2018;27(3):413–424.

    Article  Google Scholar 

  4. Elias D, Gilly F, Boutitie F, Quenet F, Bereder JM, Mansvelt B, 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(1):63–8.

    Article  Google Scholar 

  5. Kulu Y, Mueller-Stich B, Buechler MW, Ulrich A. Surgical treatment of peritoneal carcinomatosis: current treatment modalities. Langenbecks Arch Surg. 2014;399(1):41–53.

    Article  Google Scholar 

  6. Foster JM, Sleightholm R, Patel A, Shostrom V, Hall B, Neilsen B, et al. Morbidity and mortality rates following cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy compared with other high-risk surgical oncology procedures. JAMA Netw Open. 2019;2(1):e186847.

    Article  Google Scholar 

  7. Scaringi S, Leo F, Canonico G, Batignani G, Ficari F, Tonelli F. The role of cytoreductive surgery alone for the treatment of peritoneal carcinomatosis of colorectal origin. A retrospective analysis with regard to multimodal treatments. Hepatogastroenterology. 2009;56(91–92):650–5.

    Google Scholar 

  8. Sugarbaker PH, Schellinx ME, Chang D, Koslowe P, von Meyerfeldt M., Peritoneal carcinomatosis from adenocarcinoma of the colon. World J Surg. 1996;20(5): 585–91; discussion 592.

    Article  CAS  Google Scholar 

  9. 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(9):2426–32.

    Article  Google Scholar 

  10. Verwaal VJ, van Ruth S, de Bree E, van Slooten GW, van Tinteren H, Boot H, 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(20): 3737–43.

    Article  Google Scholar 

  11. Aziz O, Jaradat I, Chakrabarty B, Selvasekar CR, Fulford PE, Saunders MP, et al. Predicting survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for appendix adenocarcinoma. Dis Colon Rectum. 2018;61(7):795–802.

    Article  Google Scholar 

  12. Elias D, Laurent S, Antoun S, Duvillard P, Ducreux M, Pocard M, et al. Pseudomyxoma peritonei treated with complete resection and immediate intraperitoneal chemotherapy. Gastroenterol Clin Biol. 2003;27(4):407–12.

    PubMed  Google Scholar 

  13. Kuncewitch M, Levine EA, Shen P, Votanopoulos KI. The role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for appendiceal tumors and colorectal adenocarcinomas. Clin Colon Rectal Surg. 2018;31(5):288–294.

    Article  Google Scholar 

  14. Sugarbaker PH, Chang D, Results of treatment of 385 patients with peritoneal surface spread of appendiceal malignancy. Ann Surg Oncol. 1999;6(8):727–31.

    Article  CAS  Google Scholar 

  15. Yang XJ, Huang CQ, Suo T, Mei LJ, Yang GL, Cheng FL, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer: final results of a phase III randomized clinical trial. Ann Surg Oncol. 2011;18(6):1575–81.

    Article  Google Scholar 

  16. Baratti D, Kusamura S, Cabras AD, Bertulli R, Hutanu I, Deraco M. Diffuse malignant peritoneal mesothelioma: long-term survival with complete cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC). Eur J Cancer. 2013;49(15):3140–8.

    Article  Google Scholar 

  17. Deraco M, Casali P, Inglese MG, Baratti D, Pennacchioli E, Bertulli R, et al. Peritoneal mesothelioma treated by induction chemotherapy, cytoreductive surgery, and intraperitoneal hyperthermic perfusion. J Surg Oncol. 2003;83(3):147–53.

    Article  Google Scholar 

  18. Gupta N, Asif S, Gandhi J, Rajpurohit S, Singh S. Role of CRS and HIPEC in appendiceal and colorectal malignancies: Indian experience. Indian J Gastroenterol. 2017;36(2): 126–130.

    Article  Google Scholar 

  19. Chesnais M, Lecuru F, Mimouni M, Ngo C, Fauconnier A, Huchon C. A pre-operative predictive score to evaluate the feasibility of complete cytoreductive surgery in patients with epithelial ovarian cancer. PLoS One. 2017;12(11):e0187245.

    Article  Google Scholar 

  20. Cowan RA, Eriksson AGZ, Jaber SM, Zhou Q, Iasonos A, Zivanovic O, et al. A comparative analysis of prediction models for complete gross resection in secondary cytoreductive surgery for ovarian cancer. Gynecol Oncol. 2017;145(2): 230–5.

    Article  Google Scholar 

  21. Dineen SP, Royal RE, Hughes MS, Sagebiel T, Bhosale P, Overman M, et al. A simplified preoperative assessment predicts complete cytoreduction and outcomes in patients with low-grade mucinous adenocarcinoma of the appendix. Ann Surg Oncol. 2015;22(11):3640–6.

    Article  Google Scholar 

  22. Ghisoni E, Katsaros D, Maggiorotto F, Aglietta M, Vaira M, De Simone M, et al. A predictive score for optimal cytoreduction at interval debulking surgery in epithelial ovarian cancer: a two-centers experience. J Ovarian Res. 2018;11(1):42.

    Article  Google Scholar 

  23. Terzi C, Arslan NC, Canda AE, Peritoneal carcinomatosis of gastrointestinal tumors: where are we now? World J Gastroenterol. 2014;20(39):14371–80.

    Article  Google Scholar 

  24. Baratti D, Kusamura S, Martinetti A, Seregni E, Laterza B, Oliva DG, et al. Prognostic value of circulating tumor markers in patients with pseudomyxoma peritonei treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol. 2007;14(8): 2300–8.

    Article  Google Scholar 

  25. Baumgartner JM, et al. Predictors of progression in high-grade appendiceal or colorectal peritoneal carcinomatosis after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol. 2015;22(5):1716–21.

    Article  Google Scholar 

  26. Delhorme JB, Severac F, Averous G, Glehen O, Passot G, Bakrin N, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei of appendicular and extra-appendicular origin. Br J Surg. 2018;105(6):668–676.

    Article  Google Scholar 

  27. Govaerts K, Chandrakumaran K, Carr NJ, Cecil TD, Dayal S, Mohamed F, et al. Single centre guidelines for radiological follow-up based on 775 patients treated by cytoreductive surgery and HIPEC for appendiceal pseudomyxoma peritonei. Eur J Surg Oncol. 2018;44(9): 1371–7.

    Article  Google Scholar 

  28. Hesdorffer ME, Chabot JA, Keohan ML, Fountain K, Talbot S, Gabay M, et al. Combined resection, intraperitoneal chemotherapy, and whole abdominal radiation for the treatment of malignant peritoneal mesothelioma. Am J Clin Oncol. 2008;31(1): 49–54.

    Article  CAS  Google Scholar 

  29. Klaver CE, Musters GD, Bemelman WA, Punt CJ, Verwaal VJ, Dijkgraaf MG, et al. Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colon cancer at high risk of peritoneal carcinomatosis; the COLOPEC randomized multicentre trial. BMC Cancer. 2015;15:428.

    Article  Google Scholar 

  30. Lam JY, McConnell YJ, Rivard JD, Temple WJ, Mack LA. Hyperthermic intraperitoneal chemotherapy + early postoperative intraperitoneal chemotherapy versus hyperthermic intraperitoneal chemotherapy alone: assessment of survival outcomes for colorectal and high-grade appendiceal peritoneal carcinomatosis. Am J Surg. 2015;210(3):424–30.

    Article  Google Scholar 

  31. Loggie BW, Fleming RA, McQuellon RP, Russell GB. Prospective trial for the treatment of malignant peritoneal mesothelioma. Am Surg. 2001;67(10):999–1003.

    CAS  PubMed  Google Scholar 

  32. Solomon D, DeNicola NL, Feferman Y, Bekhor E, Reppucci ML, Feingold D, et al. More synchronous peritoneal disease but longer survival in younger patients with carcinomatosis from colorectal cancer undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol. 2019.

  33. Yan TD, Links M, Xu ZY, Kam PC, Glenn D, Morris DL. Cytoreductive surgery and perioperative intraperitoneal chemotherapy for pseudomyxoma peritonei from appendiceal mucinous neoplasms. Br J Surg. 2006;93(10):1270–6.

    Article  CAS  Google Scholar 

  34. Alexander‐Sefre F, Chandrakumaran K, Banerjee S, Sexton R, Thomas JM, Cecil T, et al. Elevated tumour markers prior to complete tumour removal in patients with pseudomyxoma peritonei predict early recurrence. Colorectal Dis. 2005;7(4):382–6.

    Article  CAS  Google Scholar 

  35. Bruno F, Baratti D, Martinetti A, Morelli D, Sottotetti E, Bonini C, et al. Mesothelin and osteopontin as circulating markers of diffuse malignant peritoneal mesothelioma: a preliminary study. Eur J Surg Oncol. 2018;44(6):792–8.

    Article  Google Scholar 

  36. Carmignani CP, Hampton R, Sugarbaker CE, Chang D, Sugarbaker PH. Utility of CEA and CA 19-9 tumor markers in diagnosis and prognostic assessment of mucinous epithelial cancers of the appendix. J Surg Oncol. 2004;87(4):162–6.

    Article  Google Scholar 

  37. Di Fabio F, Aston W, Mohamed F, Chandrakumaran K, Cecil T, Moran B. Elevated tumour markers are normalized in most patients with pseudomyxoma peritonei 7 days after complete tumour removal. Colorectal Dis. 2015;17(8):698–703.

    Article  Google Scholar 

  38. Taflampas P, Dayal S, Chandrakumaran K, Mohamed F, Cecil TD, Moran BJ. Pre-operative tumour marker status predicts recurrence and survival after complete cytoreduction and hyperthermic intraperitoneal chemotherapy for appendiceal pseudomyxoma peritonei: analysis of 519 patients. Eur J Surg Oncol. 2014;40(5):515–520.

    Article  CAS  Google Scholar 

  39. van Ruth S, Hart AA, Bonfrer JM, Verwaal VJ, Zoetmulder FA. Prognostic value of baseline and serial carcinoembryonic antigen and carbohydrate antigen 19.9 measurements in patients with pseudomyxoma peritonei treated with cytoreduction and hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol. 2002;9(10):961–7.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, 1365C Clifton Road, NE; Building C, 2nd Floor, Atlanta, GA, 30322, USA

    Mohammad Y. Zaidi MD, MS, Rachel M. Lee MD, MSPH, Adriana C. Gamboa MD, Shelby Speegle MS, Maria C. Russell MD, Shishir K. Maithel MD & Charles A. Staley III MD, FACS

  2. Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA

    Jordan M. Cloyd MD & Charles Kimbrough MD

  3. Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN, USA

    Travis Grotz MD & Jennifer Leiting MD

  4. Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Keith Fournier MD & Andrew J. Lee MD

  5. Department of Gastrointestinal Oncology, Moffitt Cancer Center, Department of Oncologic Sciences, Morsani College of Medicine, Tampa, FL, USA

    Sean Dineen MD & Sophie Dessureault MD, PhD

  6. Division of Surgical Oncology, Department of Surgery, University of California, San Diego, USA

    Kaitlyn J. Kelly MD & Nikhil V. Kotha BS

  7. Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, USA

    Callisia Clarke MD & T. Clark Gamblin MD

  8. Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Sameer H. Patel MD & Tiffany C. Lee MD

  9. Division of Surgical Oncology, Department of Surgery, University of Massachusetts Medical School, Worcester, MA, USA

    Ryan J. Hendrix MD

  10. Section of Surgical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA

    Laura Lambert MD

  11. Division of Surgical Oncology, Department of Surgery, University of Wisconsin, Madison, WI, USA

    Sean Ronnekleiv-Kelly MD & Courtney Pokrzywa MD

  12. Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA

    Andrew M. Blakely MD & Byrne Lee MD

  13. Department of Surgery, Johns Hopkins University, Baltimore, MD, USA

    Fabian M. Johnston MD, MHS & Nadege Fackche MD

Authors
  1. Mohammad Y. Zaidi MD, MS
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rachel M. Lee MD, MSPH
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Adriana C. Gamboa MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shelby Speegle MS
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jordan M. Cloyd MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Charles Kimbrough MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Travis Grotz MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jennifer Leiting MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Keith Fournier MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Andrew J. Lee MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Sean Dineen MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Sophie Dessureault MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Kaitlyn J. Kelly MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Nikhil V. Kotha BS
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Callisia Clarke MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. T. Clark Gamblin MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Sameer H. Patel MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Tiffany C. Lee MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Ryan J. Hendrix MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Laura Lambert MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Sean Ronnekleiv-Kelly MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Courtney Pokrzywa MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Andrew M. Blakely MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Byrne Lee MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Fabian M. Johnston MD, MHS
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Nadege Fackche MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. Maria C. Russell MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  28. Shishir K. Maithel MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  29. Charles A. Staley III MD, FACS
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Charles A. Staley III MD, FACS.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zaidi, M.Y., Lee, R.M., Gamboa, A.C. et al. Preoperative Risk Score for Predicting Incomplete Cytoreduction: A 12-Institution Study from the US HIPEC Collaborative. Ann Surg Oncol 27, 156–164 (2020). https://doi.org/10.1245/s10434-019-07626-y

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-019-07626-y

Search

Navigation