Skip to main content

Advertisement

SpringerLink
Log in

Outcomes and Predictive Factors of Isolated Limb Infusion for Patients with In-transit Melanoma in China

  • Melanomas
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Purpose

This study was designed to evaluate the efficacy of isolated limb infusion (ILI) treatment in Chinese patients with in-transit melanoma and to identify factors predictive of the outcome.

Methods

A total of 150 patients with in-transit melanoma who received a single ILI between 2007 and 2016 were identified from a prospectively collected database.

Results

All patients had AJCC Stages IIIb, IIIc, and IV disease. Acral lentiginous melanoma (ALM) accounted for 79% of patients, and 59% had a high burden of disease (BOD). The complete response (CR) and partial response (PR) rates were 6 and 35%, respectively. Forty-five percent of patients experienced grade III–IV limb toxicities, but no grade V toxicity was observed. Patients with a low BOD, high limb temperature, high peak creatine phosphokinase (CK) level, and grade III–IV limb toxicity achieved higher response rates. Stage IV disease and high BOD were associated with worse infield progression-free survival (PFS) and overall survival (OS), whereas patients with CR or PR to ILI had better infield PFS and OS. Multivariate analyses showed that disease stage, BOD, and a CR were independent predictors of infield PFS, whereas disease stage and a response to ILI were independent predictors of OS.

Conclusions

ILI is well-tolerated but the response rate in Chinese patients was lower than that reported in US and Australian studies. The prevalence of the ALM histological type, advanced disease stages, and a high BOD may be the main reasons for this. A response to ILI, BOD, and disease stage are prognostic factors for survival.

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.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Coit DG, Ferrone CR. Recurrent regional metastases of melanoma. In: Balch CM, Houghton AN, Sober AJ, Soong SJ, Atkins MB, Thompson JF (eds) Cutaneous melanoma, 5th edn. St. Louis: Quality Medical Publishing, 2009:487–98.

    Google Scholar 

  2. Balch CM, Gershenwald JE, Soong SJ, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol. 2009;27(36):6199–206.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Weide B, Neri D, Elia G. Intralesional treatment of metastatic melanoma: a review of therapeutic options. Cancer Immunol Immunother. 2017;66(5):647–56.

    Article  PubMed  Google Scholar 

  4. Agarwala SS. The role of intralesional therapies in melanoma. Oncology (Williston Park). 2016;30(5):436–41.

    Google Scholar 

  5. Andtbacka RH, Kaufman HL, Collichio F, et al. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol. 2015;33(25):2780–88.

    Article  CAS  PubMed  Google Scholar 

  6. Creech O, Jr., Krementz ET, Ryan RF, et al. Chemotherapy of cancer: regional perfusion utilizing an extracorporeal circuit. Ann Surg. 1958;148(4):616–32.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Lienard D, Eggermont AM, Kroon BB, et al. Isolated limb perfusion in primary and recurrent melanoma: indications and results. Semin Surg Oncol. 1998;14(3):202–09.

    Article  CAS  PubMed  Google Scholar 

  8. Moller MG, Lewis JM, Dessureault S, et al. Toxicities associated with hyperthermic isolated limb perfusion and isolated limb infusion in the treatment of melanoma and sarcoma. Int J Hyperthermia. 2008;24(3):275–89.

    Article  CAS  PubMed  Google Scholar 

  9. Thompson JF, Waugh RC, Saw RP, et al. Isolated limb infusion with melphalan for recurrent limb melanoma: a simple alternative to isolated limb perfusion. Reg Cancer Treat. 1994;7:188–92.

    Google Scholar 

  10. Kroon HM, Coventry BJ, Giles MH, et al. Australian Multicenter Study of Isolated Limb Infusion for Melanoma. Ann Surg Oncol. 2016;23(4):1096–103.

    Article  PubMed  Google Scholar 

  11. Chi Z, Li S, Sheng X, et al. Clinical presentation, histology, and prognoses of malignant melanoma in ethnic Chinese: a study of 522 consecutive cases. BMC Cancer. 2011;11:85.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Muilenburg DJ, Beasley GM, Thompson ZJ, et al. Burden of disease predicts response to isolated limb infusion with melphalan and actinomycin D in melanoma. Ann Surg Oncol. 2015;22(2):482–8.

    Article  PubMed  Google Scholar 

  13. Si L, Kong Y, Xu X, et al. Prevalence of BRAF V600E mutation in Chinese melanoma patients: large scale analysis of BRAF and NRAS mutations in a 432-case cohort. Eur J Cancer. 2012;48(1):94–100.

    Article  CAS  PubMed  Google Scholar 

  14. Beasley GM, Petersen RP, Yoo J, et al. Isolated limb infusion for in-transit malignant melanoma of the extremity: a well-tolerated but less effective alternative to hyperthermic isolated limb perfusion. Ann Surg Oncol. 2008;15(8):2195–205.

    Article  PubMed  Google Scholar 

  15. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47.

    Article  CAS  PubMed  Google Scholar 

  16. Wieberdink J, Benckhuysen C, Braat RP, et al. Dosimetry in isolation perfusion of the limbs by assessment of perfused tissue volume and grading of toxic tissue reactions. Eur J Cancer Clin Oncol. 1982;18(10):905–10.

    Article  CAS  PubMed  Google Scholar 

  17. Kroon HM, Moncrieff M, Kam PC, et al. Outcomes following isolated limb infusion for melanoma. A 14-year experience. Ann Surg Oncol. 2008;15(11):3003–13.

    Article  PubMed  Google Scholar 

  18. Brady MS, Brown K, Patel A, et al. Isolated limb infusion with melphalan and dactinomycin for regional melanoma and soft-tissue sarcoma of the extremity: final report of a phase II clinical trial. Melanoma Res. 2009;19(2):106–11.

    Article  PubMed  Google Scholar 

  19. Kroon HM, Huismans AM, Kam PC, et al. Isolated limb infusion with melphalan and actinomycin D for melanoma: a systematic review. J Surg Oncol. 2014;109(4):348–51.

    Article  CAS  PubMed  Google Scholar 

  20. Boriani F, O’Leary F, Tohill M, et al. Acral Lentiginous Melanoma—misdiagnosis, referral delay and 5 years specific survival according to site. Eur Rev Med Pharmacol Sci. 2014;18(14):1990–96.

    CAS  PubMed  Google Scholar 

  21. Hayward NK, Wilmott JS, Waddell N, et al. Whole-genome landscapes of major melanoma subtypes. Nature. 2017;545(7653):175–80.

    Article  CAS  PubMed  Google Scholar 

  22. Huismans AM, Kroon HM, Kam PC, et al. Does increased experience with isolated limb infusion for advanced limb melanoma influence outcome? A comparison of two treatment periods at a single institution. Ann Surg Oncol. 2011;18(7):1877–83.

    Article  PubMed  Google Scholar 

  23. Lindner P, Doubrovsky A, Kam PC, et al. Prognostic factors after isolated limb infusion with cytotoxic agents for melanoma. Ann Surg Oncol. 2002;9(2):127–36.

    Article  PubMed  Google Scholar 

  24. Steinman J, Ariyan C, Rafferty B, et al. Factors associated with response, survival, and limb salvage in patients undergoing isolated limb infusion. J Surg Oncol. 2014;109(5):405–9.

    Article  PubMed  Google Scholar 

  25. Vrouenraets BC, Nieweg OE, Kroon BB. Thirty-five years of isolated limb perfusion for melanoma: indications and results. Br J Surg. 1996;83(10):1319–28.

    Article  CAS  PubMed  Google Scholar 

  26. Kroon HM, Moncrieff M, Kam PC, et al. Factors predictive of acute regional toxicity after isolated limb infusion with melphalan and actinomycin D in melanoma patients. Ann Surg Oncol. 2009;16(5):1184–92.

    Article  PubMed  Google Scholar 

  27. Kroon HM, Lin DY, Kam PC, et al. Isolated limb infusion as palliative treatment for advanced limb disease in patients with AJCC stage IV melanoma. Ann Surg Oncol. 2009;16(5):1193–201.

    Article  PubMed  Google Scholar 

  28. Chang CJ, Tai KF, Roffler S, et al. The immunization site of cytokine-secreting tumor cell vaccines influences the trafficking of tumor-specific T lymphocytes and antitumor efficacy against regional tumors. J Immunol. 2004;173(10):6025–32.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgement

The authors are very grateful to Dr. Jonathan S. Zager, Moffitt Cancer Center, for helping with the proof reading of our manuscript. We also thank Dr. Mary S. Brady from the Memorial Sloan-Kettering Cancer Center who taught us the ILI technique and allowed us to use Excel-based software to calculate limb volumes.

Funding

This work was supported by grants from Major State Basic Research Development Program of China (2013CB911004) Beijing Talents Fund (2014000021223ZK26), Beijing Bai-Qian-Wan Talents Project, Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (ZYLX201603) and Beijing Municipal Science & Technology Commission (Z151100003915074).

Author information

Author notes

  1. Siming Li and Xinan Sheng contributed equally to this work and are the co-first authors.

Authors and Affiliations

  1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Collaborative Innovation Center of Cancer Medicine, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China

    Siming Li MD, Xinan Sheng MD, Lu Si MD, Chuanliang Cui MD, Yan Kong PhD, Lili Mao MD, Bin Lian MD, Bixia Tang MD, Xieqiao Yan MD, Xuan Wang MD, Zhihong Chi MD & Jun Guo MD

  2. Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China

    Zhihong Chi MD & Jun Guo MD

Authors
  1. Siming Li MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xinan Sheng MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lu Si MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chuanliang Cui MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yan Kong PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lili Mao MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bin Lian MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Bixia Tang MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xieqiao Yan MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Xuan Wang MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Zhihong Chi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Jun Guo MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Zhihong Chi MD or Jun Guo MD.

Ethics declarations

Disclosure

None.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, S., Sheng, X., Si, L. et al. Outcomes and Predictive Factors of Isolated Limb Infusion for Patients with In-transit Melanoma in China. Ann Surg Oncol 25, 885–893 (2018). https://doi.org/10.1245/s10434-017-6256-x

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-017-6256-x

Keywords

Search

Navigation