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International Multicenter Experience of Isolated Limb Infusion for In-Transit Melanoma Metastases in Octogenarian and Nonagenarian Patients

  • Melanoma
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Abstract

Background

Isolated limb infusion (ILI) is used to treat in-transit melanoma metastases confined to an extremity. However, little is known about its safety and efficacy in octogenarians and nonagenarians (ON).

Patients and Methods

ON patients (≥ 80 years) who underwent a first ILI for American Joint Committee on Cancer seventh edition stage IIIB/IIIC melanoma between 1992 and 2018 at nine international centers were included and compared with younger patients (< 80 years). A cytotoxic drug combination of melphalan and actinomycin-D was used.

Results

Of the 687 patients undergoing a first ILI, 160 were ON patients (median age 84 years; range 80–100 years). Compared with the younger cohort (n = 527; median age 67 years; range 29–79 years), ON patients were more frequently female (70.0% vs. 56.9%; p = 0.003), had more stage IIIB disease (63.8 vs. 53.3%; p = 0.02), and underwent more upper limb ILIs (16.9% vs. 9.5%; p = 0.009). ON patients experienced similar Wieberdink limb toxicity grades III/IV (25.0% vs. 29.2%; p = 0.45). No toxicity-related limb amputations were performed. Overall response for ON patients was 67.3%, versus 64.6% for younger patients (p = 0.53). Median in-field progression-free survival was 9 months for both groups (p = 0.88). Median distant progression-free survival was 36 versus 23 months (p = 0.16), overall survival was 29 versus 40 months (p < 0.0001), and melanoma-specific survival was 46 versus 78 months (p = 0.0007) for ON patients compared with younger patients, respectively.

Conclusions

ILI in ON patients is safe and effective with similar response and regional control rates compared with younger patients. However, overall and melanoma-specific survival are shorter.

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References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67:7–30.

    Article  Google Scholar 

  2. Whiteman DC, Green AC, Olsen CM. The growing burden of invasive melanoma: projections of incidence rates and numbers of new cases in six susceptible populations through 2031. J Invest Dermatol. 2016;136:1161–71.

    Article  CAS  Google Scholar 

  3. Paulson KG, Gupta D, Kim TS, et al. Age-specific incidence of melanoma in the United States. JAMA Dermatol. 2019. https://doi.org/10.1001/jamadermatol.2019.3353.

    Article  PubMed  Google Scholar 

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

    Article  Google Scholar 

  5. Sanki A, Kroon HM, Kam PC, Thompson JF. Isolated limb perfusion and isolated limb infusion for malignant lesions of the extremities. Curr Probl Surg. 2011;48:371–430.

    Article  Google Scholar 

  6. Eggermont A, Blank CU, Mandala M, et al. Adjuvant pembrolizumab versus placebo in resected stage III melanoma. N Engl J Med. 2018;378:1789–801.

    Article  CAS  Google Scholar 

  7. Miura JT, Kroon HM, Beasley GM, et al. Long-term oncologic outcomes after isolated limb infusion for locoregionally metastatic melanoma: an international multicenter analysis. Ann Surg Oncol. 2019;26:2486–94.

    Article  Google Scholar 

  8. Kroon HM, Coventry BJ, Giles MH, et al. Safety and efficacy of isolated limb infusion chemotherapy for advanced locoregional melanoma in elderly patients: an Australian multicentre study. Ann Surg Oncol. 2017;24:3245–51.

    Article  Google Scholar 

  9. Kroon HM, Huismans A, Waugh RC, et al. Isolated limb infusion: technical aspects. J Surg Oncol. 2014;109:352–6.

    Article  Google Scholar 

  10. 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;15:2195–205.

    Article  Google Scholar 

  11. 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;18:905–10.

    Article  CAS  Google Scholar 

  12. 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;45:228–47.

    Article  CAS  Google Scholar 

  13. Hunter RD. World Health Organization (WHO) handbook for reporting results of cancer treatment. Geneva: WHO; 1979.

    Google Scholar 

  14. Madu MF, Deken MM, van der Hage JA, et al. Isolated limb perfusion for melanoma is safe and effective in elderly patients. Ann Surg Oncol. 2017;24:1997–2005.

    Article  Google Scholar 

  15. Kroon HM, Lin DY, Kam PC, Thompson JF. Safety and efficacy of isolated limb infusion with cytotoxic drugs in elderly patients with advanced locoregional melanoma. Ann Surg. 2009;249:1008–13.

    Article  Google Scholar 

  16. Noorda EM, Vrouenraets BC, Nieweg OE, van Geel AN, Eggermont AM, Kroon BB. Safety and efficacy of isolated limb perfusion in elderly melanoma patients. Ann Surg Oncol. 2002;9:968–74.

    Article  CAS  Google Scholar 

  17. Kroon HM, Coventry BJ, Henderson MA, et al. Evaluation of the efficacy and toxicity of upper extremity isolated limb infusion chemotherapy for melanoma: an Australian multi-center study. Eur J Surg Oncol. 2019;45:832–7.

    Article  Google Scholar 

  18. World Health Organization. Countries [Internet]. Geneva: World Health Organization; 2019 [cited 2019 October 27]. www.who.int/countries/en/.

  19. Montecino-Rodriguez E, Berent-Maoz B, Dorshkind K. Causes, consequences, and reversal of immune system aging. J Clin Invest. 2013,123:958–65.

    Article  CAS  Google Scholar 

  20. Aunan JR, Cho WC, Soreide K. The biology of aging and cancer: a brief overview of shared and divergent molecular hallmarks. Aging Dis. 2017,8:628–42.

    Article  Google Scholar 

  21. Eggermont AMM, Chiarion-Sileni V, Grob JJ, et al. Prolonged survival in stage III melanoma with Ipilimumab adjuvant therapy. N Engl J Med. 2016;375:1845–55.

    Article  CAS  Google Scholar 

  22. National Comprehensive Cancer Network (NCCN). Clinical practice guidelines in oncology: cutaneous melanoma, version 2.2019. JNCCN. 2019;17:367–402.

    Google Scholar 

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

    Article  Google Scholar 

  24. Wernick BD, Goel N, Zih FSW, Farma JM. A surgical perspective report on melanoma management. Melanoma Manag. 2017;4:105–12.

    Article  Google Scholar 

  25. Boyd KU, Wehrli BM, Temple CL. Intra-lesional interleukin-2 for the treatment of in-transit melanoma. J Surg Oncol. 2011;104:711–7.

    Article  CAS  Google Scholar 

  26. Antbacka RH; Kaufman HL, Collichio F, et al. Talimogene laherparepvec improves durable response rat in patients with advanced melanoma. J Clin Oncol. 2015;33:2780–8.

    Article  Google Scholar 

  27. Moreno-Ramirez D, Cruz-Merino, L, Ferrandiz L, Villegas-Portero R, Nieto-Garcia A. Isolated limb perfusion for malignant melanoma: systemic review on effectiveness and safety. Oncologist. 2010;15:416–27.

    Article  Google Scholar 

  28. Kroon HM. Treatment of locally advanced melanoma by isolated limb infusion with cytotoxic drugs. J Skin Cancer. 2011;2011:106573.

    Article  Google Scholar 

  29. Weitman ES, Zager JS. Regional therapies for locoregionally advanced and unresectable melanoma. Clin Exp Metastasis. 2018;35:495–502.

    Article  CAS  Google Scholar 

  30. Luu C, Khushalani NI, Zager JS. Intralesional and systemic immunotherapy for metastatic melanoma. Expert Opin Biol Ther. 2016;16:1491–9.

    Article  CAS  Google Scholar 

  31. Weber J, Mandala M, Del Vecchio M, et al. Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma. N Engl J Med. 2017;377:1824–35.

    Article  CAS  Google Scholar 

  32. Beasley GM, Caudle A, Petersen RP, et al. A multi-institutional experience of isolated limb infusion: defining response and toxicity in the US. J Am Coll Surg. 2009;208:706–15.

    Article  Google Scholar 

  33. Kroon HM, Lin DY, Kam PC, Thompson JF. Isolated limb infusion as palliative treatment for advanced limb disease in patients with AJCC stage IV melanoma. Ann Surg Oncol. 2009;16:1193–201.

    Article  Google Scholar 

  34. Beasley GM, Coleman AP, Raymond A, et al. A phase I multi-institutional study of systemic sorafenib in conjunction with regional melphalan for in-transit melanoma of the extremity. Ann Surg Oncol. 2012;19:3896–905.

    Article  CAS  Google Scholar 

  35. Ariyan CE, Brady MS, Siegelbaum RH, et al. Robust antitumor responses result from local chemotherapy and CTLA-4 blockade. Cancer Immunol Res. 2018;6:189–200.

    Article  CAS  Google Scholar 

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Correspondence to Hidde M. Kroon MD, PhD.

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Disclosures

J.S.Z. Patent for high-flow ILI. J.F.T. GlaxoSmithKline and Provectus Inc.: honoraria and travel support for Advisory Board participation. B.M.S. Australia and MSD Australia: honoraria for Advisory Board participation.

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Teras, J., Kroon, H.M., Miura, J.T. et al. International Multicenter Experience of Isolated Limb Infusion for In-Transit Melanoma Metastases in Octogenarian and Nonagenarian Patients. Ann Surg Oncol 27, 1420–1429 (2020). https://doi.org/10.1245/s10434-020-08312-0

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  • DOI: https://doi.org/10.1245/s10434-020-08312-0

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