Advertisement

Health-Related Quality of Life After Cytoreductive Surgery/HIPEC for Mucinous Appendiceal Cancer: Results of a Multicenter Randomized Trial Comparing Oxaliplatin and Mitomycin

  • Omeed Moaven
  • Konstantinos I. Votanopoulos
  • Perry Shen
  • Paul Mansfield
  • David L. Bartlett
  • Greg Russell
  • Richard McQuellon
  • John H. Stewart
  • Edward A. LevineEmail author
Peritoneal Surface Malignancy
  • 70 Downloads

Abstract

Background

This study evaluated health-related quality of life (HRQOL) using patient-reported outcomes in subjects with mucinous appendiceal neoplasms who underwent cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) as part of a randomized trial comparing mitomycin with oxaliplatin.

Methods

In this prospective multicenter study, 121 mucinous appendiceal cancer patients, with evidence of peritoneal dissemination who underwent CRS, were randomized to receive mitomycin (divided 40 mg) or oxaliplatin (200 mg/m2) for HIPEC. The Functional Assessment of Cancer Therapy Neurotoxicity (FACT-G/NTX) questionnaire was utilized to assess HRQOL. The Trial Outcome Index (TOI) is a summary index responsive to changes in physical/functional outcomes. Repeated measures mixed models with an unstructured variance matrix were applied to assess changes in HRQOL longitudinally.

Results

Baseline questionnaire compliance was 95.9%. Baseline physical well-being (PWB) was independently associated with overall survival (hazard ratio 0.79, 95% confidence interval 0.66–0.96; p = 0.017). The TOI was significantly lower in the mitomycin group compared with the oxaliplatin arm at 12 weeks (p = 0.044; score difference 6.35) and 24 weeks after surgery (p = 0.049; score difference 5.61). At 12 weeks after surgery, declines from baseline were significant in the TOI (p = 0.004; score decline 8.99), PWB (p < 0.001; score decline 2.83), and FWB (p < 0.001; score decline 3.42) in the mitomycin group but not the oxaliplatin group.

Conclusions

Compared with mitomycin, HIPEC perfusion with oxaliplatin results in significantly better physical and functional outcomes. With similar survival outcomes and complication rates, oxaliplatin should be considered as the chemoperfusion agent of choice in mucinous appendiceal cancer patients undergoing CRS/HIPEC.

Notes

Funding

This study was supported in part by the Orin Smith Family Fund, National Cancer Institute Grant Number P30CA012197 to Wake Forest Comprehensive Cancer Center (WFCCC), and the biostatistical and clinical cores facilities of the WFCCC.

Disclosures

Omeed Moaven, Konstantinos I. Votanopoulos, Perry Shen, Paul Mansfield, David L. Bartlett, Greg Russell, Richard McQuellon, John H. Stewart, and Edward A. Levine have no disclosures to declare.

Supplementary material

10434_2019_8064_MOESM1_ESM.docx (916 kb)
Supplementary material 1 (DOCX 915 kb)

References

  1. 1.
    Votanopoulos KI, Russell G, Randle RW, Shen P, Stewart JH, Levine EA. Peritoneal surface disease (PSD) from appendiceal cancer treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC): overview of 481 cases. Ann Surg Oncol. 2015;22(4):1274–9.CrossRefGoogle Scholar
  2. 2.
    Mogal HD, Levine EA, Russell G, Shen P, Stewart JH, Votanopoulos KI. Conditional survival after cytoreductive surgery with heated intraperitoneal chemotherapy for low- and high-grade appendiceal primaries. Ann Surg Oncol. 2016;23(2):534–8.CrossRefGoogle Scholar
  3. 3.
    Wagner PL, Austin F, Maduekwe U, et al. Extensive cytoreductive surgery for appendiceal carcinomatosis: morbidity, mortality, and survival. Ann Surg Oncol. 2013;20(4):1056–62.CrossRefGoogle Scholar
  4. 4.
    Dodson RM, McQuellon RP, Mogal HD, et al. Quality-of-life evaluation after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol. 2016;23(Suppl 5):772–83.CrossRefGoogle Scholar
  5. 5.
    Langenhoff BS, Krabbe PF, Wobbes T, Ruers TJ. Quality of life as an outcome measure in surgical oncology. Br J Surg. 2001;88(5):643–52.CrossRefGoogle Scholar
  6. 6.
    Au HJ, Ringash J, Brundage M, et al. Added value of health-related quality of life measurement in cancer clinical trials: the experience of the NCIC CTG. Exp Rev Pharmacoecon Outcomes Res. 2010;10(2):119–28.CrossRefGoogle Scholar
  7. 7.
    Quinten C, Coens C, Mauer M, et al. Baseline quality of life as a prognostic indicator of survival: a meta-analysis of individual patient data from EORTC clinical trials. Lancet Oncol. 2009;10(9):865–71.CrossRefGoogle Scholar
  8. 8.
    Outcomes of cancer treatment for technology assessment and cancer treatment guidelines. American Society of Clinical Oncology. J Clin Oncol. 1996;14(2):671–9.Google Scholar
  9. 9.
    Osoba D. Health-related quality of life and cancer clinical trials. Ther Adv Med Oncol. 2011;3(2):57–71.CrossRefGoogle Scholar
  10. 10.
    Bascoul-Mollevi C, Gourgou S, Galais MP, et al. Health-related quality of life results from the PRODIGE 5/ACCORD 17 randomised trial of FOLFOX versus fluorouracil-cisplatin regimen in oesophageal cancer. Eur J Cancer. 2017;84:239–49.CrossRefGoogle Scholar
  11. 11.
    Gotay CC, Kawamoto CT, Bottomley A, Efficace F. The prognostic significance of patient-reported outcomes in cancer clinical trials. J Clin Oncol. 2008;26(8):1355–63.CrossRefGoogle Scholar
  12. 12.
    Levine EA, Votanopoulos KI, Shen P, et al. A multicenter randomized trial to evaluate hematologic toxicities after hyperthermic intraperitoneal chemotherapy with oxaliplatin or mitomycin in patients with appendiceal tumors. J Am Coll Surg. 2018;226(4):434–43.CrossRefGoogle Scholar
  13. 13.
    Calhoun EA, Welshman EE, Chang CH, et al. Psychometric evaluation of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (Fact/GOG-Ntx) questionnaire for patients receiving systemic chemotherapy. Int J Gynecol Cancer. 2003;13(6):741–8.PubMedGoogle Scholar
  14. 14.
    Huang HQ, Brady MF, Cella D, Fleming G. Validation and reduction of FACT/GOG-Ntx subscale for platinum/paclitaxel-induced neurologic symptoms: a gynecologic oncology group study. Int J Gynecol Cancer. 2007;17(2):387–93.CrossRefGoogle Scholar
  15. 15.
    Jaeschke R, Singer J, Guyatt GH. Measurement of health status. Ascertaining the minimal clinically important difference. Control Clin Trials. 1989;10(4):407–15.CrossRefGoogle Scholar
  16. 16.
    Trask PC, Hsu MA, McQuellon R. Other paradigms: health-related quality of life as a measure in cancer treatment: its importance and relevance. Cancer J. 2009;15(5):435–40.CrossRefGoogle Scholar
  17. 17.
    Ihemelandu CU, McQuellon R, Shen P, Stewart JH, Votanopoulos K, Levine EA. Predicting postoperative morbidity following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CS + HIPEC) with preoperative FACT-C (Functional Assessment of Cancer Therapy) and patient-rated performance status. Ann Surg Oncol. 2013;20(11):3519–26.CrossRefGoogle Scholar
  18. 18.
    Seretis C, Youssef H. Quality of life after cytoreductive surgery and intraoperative hyperthermic intraperitoneal chemotherapy for peritoneal surface malignancies: a systematic review. Eur J Surg Oncol. 2014;40(12):1605–13.CrossRefGoogle Scholar
  19. 19.
    Shan LL, Saxena A, Shan BL, Morris DL. Quality of life after cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy for peritoneal carcinomatosis: a systematic review and meta-analysis. Surg Oncol. 2014;23(4):199–210.CrossRefGoogle Scholar
  20. 20.
    Leung V, Huo YR, Liauw W, Morris DL. Oxaliplatin versus Mitomycin C for HIPEC in colorectal cancer peritoneal carcinomatosis. Eur J Surg Oncol. 2017;43(1):144–9.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;110(7):779–85.CrossRefGoogle Scholar
  22. 22.
    Glockzin G, von Breitenbuch P, Schlitt HJ, Piso P. Treatment-related morbidity and toxicity of CRS and oxaliplatin-based HIPEC compared to a mitomycin and doxorubicin-based HIPEC protocol in patients with peritoneal carcinomatosis: a matched-pair analysis. J Surg Oncol. 2013;107(6):574–8.CrossRefGoogle Scholar
  23. 23.
    Hompes D, D’Hoore A, Wolthuis A, 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(6):527–32.CrossRefGoogle Scholar
  24. 24.
    van Eden WJ, Kok NFM, Woensdregt K, Huitema ADR, Boot H, Aalbers AGJ. Safety of intraperitoneal Mitomycin C versus intraperitoneal oxaliplatin in patients with peritoneal carcinomatosis of colorectal cancer undergoing cytoreductive surgery and HIPEC. Eur J Surg Oncol. 2018;44(2):220–7.CrossRefGoogle Scholar
  25. 25.
    Votanopoulos K, Ihemelandu C, Shen P, Stewart J, Russell G, Levine EA. A comparison of hematologic toxicity profiles after heated intraperitoneal chemotherapy with oxaliplatin and mitomycin C. J Surg Res. 2013;179(1):e133–9.CrossRefGoogle Scholar
  26. 26.
    Rouers A, Laurent S, Detroz B, Meurisse M. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal carcinomatosis: higher complication rate for oxaliplatin compared to Mitomycin C. Acta Chir Belg. 2006;106(3):302–6.CrossRefGoogle Scholar
  27. 27.
    Bonnetain F, Fiteni F, Efficace F, Anota A. Statistical challenges in the analysis of health-related quality of life in cancer clinical trials. J Clin Oncol. 2016;34(16):1953–6.CrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2019

Authors and Affiliations

  • Omeed Moaven
    • 1
  • Konstantinos I. Votanopoulos
    • 1
  • Perry Shen
    • 1
  • Paul Mansfield
    • 3
  • David L. Bartlett
    • 2
  • Greg Russell
    • 1
  • Richard McQuellon
    • 1
  • John H. Stewart
    • 4
  • Edward A. Levine
    • 1
    • 5
    Email author
  1. 1.Department of SurgeryWake Forest UniversityWinston SalemUSA
  2. 2.Department of SurgeryUniversity of Pittsburgh Medical CenterPittsburghUSA
  3. 3.Department of Surgical OncologyMD Anderson Cancer CenterHoustonUSA
  4. 4.Department of SurgeryUniversity of IllinoisChicagoUSA
  5. 5.Section of Surgical Oncology, Department of General SurgeryWake Forest Baptist HealthWinston SalemUSA

Personalised recommendations