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Survival After Induction Chemotherapy and Surgical Resection for High-Grade Soft Tissue Sarcoma. Is Radiation Necessary?

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Abstract

Background: Induction chemotherapy can produce dramatic necrosis in sarcomas—raising the question of whether or not radiation is necessary. This study reviews the clinical outcome of a subset of patients with high-grade extremity soft tissue sarcomas (STS) who were treated with induction chemotherapy and surgical resection but without radiation.

Methods: Nonmetastatic, large, high-grade STS of the pelvis and extremities were treated with intra-arterial cisplatin, adriamycin, and, after 1995, ifosfamide. After induction, oncologic resection and histologic evaluation were performed. Good responders with good surgical margins were not treated with radiation.

Results: Thirty-three patients, with a median follow-up of 5 years, were included. Limb salvage rate was 94%. Median tumor necrosis was 95%. Four patients developed metastatic disease with three subsequent deaths. Two local recurrences occurred; both patients were salvaged with re-resection and adjuvant external beam radiotherapy, although one died of metastatic disease 10 years later. Relapse-free and overall survival is 80% and 88% at 5 and 10 years by Kaplan-Meier analysis.

Conclusions: Intensive induction chemotherapy can be extremely effective for high-grade STS, permitting limb-sparing surgery in lieu of amputation. Radiation may not be necessary if a good response to induction chemotherapy and negative wide margins are achieved. All patients with large, deep, high-grade STS of the extremities should be considered candidates for induction chemotherapy.

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REFERENCES

  1. Eilber F, Giuliano A, Eckardt J, Patterson K, Moseley S, Goodnight J. Adjuvant chemotherapy for osteosarcoma: A randomized prospective trial. J Clin Oncol 1987; 5: 21–26.

    PubMed  CAS  Google Scholar 

  2. Link MP, Goorin AM, Horowitz M, et al. Adjuvant chemotherapy of high-grade osteosarcoma of the extremity: Updated results of the multi-institutional osteosarcoma study. Clin Orthop 1991; 270: 8–14.

    PubMed  Google Scholar 

  3. Limb-sparing treatment of adult soft-tissue sarcomas and osteosarcomas. NIH Consensus Statement, Bethesda, MD, Dec 3–5, 1984. 5:1–7.

  4. Gherlinzoni F, Picci P, Bacci G, Campanacci D. Limb sparing versus amputation in osteosarcoma. Correlation between local control, surgical margins and tumor necrosis: Istituto Rizzoli experience. Ann Oncol 1992; 3: S23–27.

    PubMed  Google Scholar 

  5. Rougraff BT, Simon MA, Kneisl JS, Greenberg DB, Mankin HJ. Limb salvage compared with amputation for osteosarcoma of the distal end of the femur: A long term oncological, functional, and quality of life study. J Bone Joint Surg 1994; 76A: 649–56.

    Google Scholar 

  6. Picci P, Sangiorgi L, Rougraff BT, Neff JR, Casadei R, Campanacci M. Relationship of chemotherapy-induced necrosis and surgical margins to local recurrence in osteosarcoma. J Clin Oncol 1994; 12: 2699–2705.

    CAS  PubMed  Google Scholar 

  7. Davis AM, Bell PJ. Prognostic factors in osteosarcoma: A critical review. J Clin Oncol 1994; 12: 423–31.

    CAS  PubMed  Google Scholar 

  8. Malawer MM, Link MP, Donaldson SS. Sarcomas of Bone: Radiation therapy in the treatment of osteosarcoma.In: Devita VT, Hellman S, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 5th ed., New York: Lippincot-Raven, 1997: 1833–4.

    Google Scholar 

  9. Williard WC, Hajdu SI, Casper ES, Brennan MF. Comparison of amputation with limb sparing operations for adult soft tissue sarcoma of the extremity. Ann Surg 1992; 215: 269–275.

    Article  PubMed  CAS  Google Scholar 

  10. Beech DJ, Pollock RE. Surgical management of primary soft tissue sarcomas. Hematol Oncol Clin North Am 1995; 9: 707–718.

    PubMed  CAS  Google Scholar 

  11. Singer S, Corson JM, Gonin R, Labow B, Eberlein TJ. Prognostic factors predictive of survival and local recurrence for extremity soft tissue sarcoma. Ann Surg 1994; 219: 165–173.

    PubMed  CAS  Google Scholar 

  12. Talbert ML, Zagars GK, Sherman NE, Rhomsdahl MM. Conservative surgery and radiation therapy for soft tissue sarcoma of the wrist, hand, ankle and foot. Cancer 1990; 66: 2482–2491.

    PubMed  CAS  Google Scholar 

  13. Suit HD, Spiro I. Radiation as a therapeutic modality in sarcomas of the soft tissue. Hematol Oncol Clin North Am 1995; 9: 733–746.

    PubMed  CAS  Google Scholar 

  14. Harrison LB, Janjan N. Brachytherapy in sarcomas. Hematol Oncol Clin North Am 1995; 9: 747–763.

    PubMed  CAS  Google Scholar 

  15. Sadoski C, Suit HD, Rosenberg A, Mankin H, Efird J. Preoperative radiation, surgical margins and local control of extremity sarcomas of soft tissue. J Surg Oncol 1993; 5: 223–230.

    Google Scholar 

  16. Benjamin RS, Wiernik PH, Bachur NR. Adriamycin. A new effective agent in the therapy of disseminated sarcomas. Med Pediatr Oncol 1975; 1: 63–76.

    PubMed  CAS  Google Scholar 

  17. Creagan ET, Hahn RG, Ahmann DL, Bisel HF. A clinical trial of adriamycin (NSC 123127) in advanced sarcomas. Oncology 1977; 34: 90–1.

    Article  PubMed  CAS  Google Scholar 

  18. Samson MK, Baker LH, Benjamin RS, Lane M, Plager C. Cis-dichlorodiamine-platinum (II) in Advanced Soft Tissue and Bony Sarcomas. A Southwest Oncology Group Study. Cancer Treat Rep 1979; 63: 2027–9.

    PubMed  CAS  Google Scholar 

  19. Karakousis CP, Holtermann OA, Holyoke ED. Cis-dichlorodiamine-platinum (II) in Metastatic Soft Tissue Sarcomas. Cancer Treat Rep 1979; 63: 2071–5.

    PubMed  CAS  Google Scholar 

  20. Brenner J, Magill GB, Sordillo PP, Cheng EW, Yagoda A. Phase II Trial of Cisplatin (CPDD) in Previously Treated Patients with Advanced Soft Tissue Sarcomas. Cancer 1982; 50: 2031–3.

    PubMed  CAS  Google Scholar 

  21. Jelic S, Koucin V, Milanovic N, et al. Randomized study of high-dose epirubicin versus high-dose epirubicin-cisplatin chemotherapy for advanced soft tissue sarcoma. Eur J Cancer 1997; 33: 220–225.

    PubMed  CAS  Google Scholar 

  22. Elias A, Ryan L, Sulkes A, Collins J, Aisner J, Antman KH. Response to mesna, doxorubicin, ifosfamide, and dacarbazine in 108 Patients with metastatic or unresectable sarcoma and no prior chemotherapy. J Clin Oncol 1989; 7: 1208–1216.

    PubMed  CAS  Google Scholar 

  23. Bramwell V, Quirt I, Warr D, et al. Combination chemotherapy with doxorubicin, dacarbazine, and ifosfamide in advanced adult soft tissue sarcoma. J Natl Cancer Inst 1989; 81: 1496–1499.

    PubMed  CAS  Google Scholar 

  24. Santoro A, Rouesse J, Steward W, et al. A randomized EORTC study in advanced soft tissue sarcoma (STS): ADM vs ADM + IFX vs CYVADIC. Proc Annu Meet Am Soc Clin Oncol 1990; 9: A1196.

    Google Scholar 

  25. Edmonson JH, Ryan LM, Blum RH, et al. Randomized comparison of doxorubicin alone versus ifosfamide plus doxorubicin or mitomycin, doxorubicin, and cisplatin against advanced soft tissue sarcomas. J Clin Oncol 1993; 11: 1269–75.

    PubMed  CAS  Google Scholar 

  26. Azzarelli A, Quagluiolo V, Casali F, Fissi S, Montalto F, Santoro A. Preoperative doxorubicin plus ifosfamide in primary soft tissue sarcomas of the extremities. Cancer Chemother Pharmacol 1993; 31: S210–2.

    PubMed  Google Scholar 

  27. Demetri GD, Elias AD. Results of single-agent and combination chemotherapy for advanced soft tissue sarcomas. Hematol Oncol Clin North Am 1995; 9: 3: 765–785.

    PubMed  CAS  Google Scholar 

  28. Patel SR, Vadjan-Raj S, Burgess MA, et al. Results of two consecutive trials of dose intensive chemotherapy with doxorubicin and ifosfamide in patients with sarcomas. Am J Clin Oncol 1998; 21: 317–321.

    PubMed  CAS  Google Scholar 

  29. Patel SR, Benjamin RS. New chemotherapeutic strategies for soft tissue sarcomas. Semin Surg Oncol 1999; 17: 47–51.

    PubMed  CAS  Google Scholar 

  30. Henshaw RM, Valente A, Shmookler BM, Priebat D, Malawer MM. (Paper 180) Limb salvage, histologic necrosis and disease free survival for unresectable soft tissue sarcomas treated with neoadjuvant intra-arterial chemotherapy and attempted surgical resection. Paper presented at: 64th Annual Meeting of the American Academy of Orthopaedic Surgeons; February 1997; San Francisco, CA.

  31. Casper ES, Gaynor JJ, Hajdu SI, et al. A prospective randomized trial of adjuvant chemotherapy with bolus versus continuous infusion of doxorubicin in patients with high-grade extremity soft tissue sarcoma and an analysis of prognostic factors. Cancer 1991; 68: 1221–1229.

    PubMed  CAS  Google Scholar 

  32. Chan HG, Gross JF. Intra-arterial infusion of anti-cancer drugs: theoretic aspects of drug delivery and review of responses. Cancer Treat Rep 1980; 64: 31.

    Google Scholar 

  33. Mavligit GM, Benjamin R, Patt YZ, et al. Intraarterial cis-platinum for patients with inoperable skeletal tumors. Cancer 1981; 48: 1–4.

    PubMed  CAS  Google Scholar 

  34. Jaffe N, Knapp J, Chuang VP. Osteosarcoma. Intra-arterial treatment of the primary tumor with cis-diammine-dichloroplatinum II (CDP). Angiographic, pathologic, and pharmacologic studies. Cancer 1983; 51: 402–407.

    CAS  PubMed  Google Scholar 

  35. Priebat D, Malawer MM, Markan Y, et al. Clinical outcome of neoadjuvant intraarterial cisplatin and continuous intravenous infusion adriamycin for large high-grade unresectable/borderline soft tissue sarcomas of the extremities. Proc Annu Meet Am Soc Clin Oncol 1994; 13: A1648.

    Google Scholar 

  36. Chang AE, Kinsella T, Glatstein E, et al. Adjuvant chemotherapy for patients with high-grade soft tissue sarcomas of the extremity. J Clin Oncol 1988; 6: 1491–1500.

    PubMed  CAS  Google Scholar 

  37. Gherlinzoni F, Picca P, Bacci G, et al. Late results of a randomized trial for the treatment of soft tissue sarcomas (STS) of the extremities in adult patients. Proc Annu Meet Am Soc Clin Oncol 1993; 12: A1633.

    Google Scholar 

  38. Bramwell V, Rouesse J, Steward W, et al. Adjuvant CYVADIC chemotherapy for adult soft tissue sarcoma-reduced local recurrence but no improvement in survival: a study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. J Clin Oncol 1994; 12: 1137–49.

    PubMed  CAS  Google Scholar 

  39. Mertens WC, Bramwell VH. Adjuvant chemotherapy in the treatment of soft tissue sarcoma. Clin Orthop 1993; 289: 81–93.

    PubMed  Google Scholar 

  40. Zalupski MM, Baker LH. Systemic adjuvant chemotherapy for soft tissue sarcomas. Hematol Oncol Clin North Am 1995; 9: 787–800.

    PubMed  CAS  Google Scholar 

  41. Tierney JF, Mosseri V, Stewart LA, Souhami RL, Parmar MK. Adjuvant chemotherapy for soft-tissue sarcoma: review and meta-analysis of the published results of randomised clinical trials. Br J Cancer 1995; 72: 469–75.

    PubMed  CAS  Google Scholar 

  42. Tierney JF. Adjuvant chemotherapy for localized unresectable soft tissue sarcoma of adults. Meta-analysis of individualized data. Lancet 1997; 350: 1647–1654.

    Article  PubMed  Google Scholar 

  43. Frustaci S, Gherlinzoni F, De Pauli A, et al. Preliminary results of an adjuvant randomized trial on high risk extremity soft tissue sarcomas (STS). The interim analysis. Proc Annu Meet Am Soc Clin Oncol 1997; 16: A1785.

    Google Scholar 

  44. Frustaci S, Gherlinzoni F, De Pauli A, et al. Maintenance of efficacy of adjuvant chemotherapy in soft tissue sarcoma of the extremities. Update of a randomized trial. Proc Annu Meet Am Soc Clin Oncol 1999; 18: A2108.

    Google Scholar 

  45. Rouesse JG, Friedman S, Sevin DM, et al. Preoperative induction chemotherapy in the treatment of locally advanced soft tissue sarcomas. Cancer 1987; 60: 296–300.

    PubMed  CAS  Google Scholar 

  46. Pezzi CM, Pollock RE, Evans HL, et al. Preoperative chemotherapy for soft tissue sarcomas of the extremities. Ann Surg 1990; 211: 476–481.

    PubMed  CAS  Google Scholar 

  47. Rahoty P, Konya A. Results of preoperative neoadjuvant chemotherapy and surgery in the management of patients with soft tissue sarcoma. Eur J Surg Oncol 1993; 19: 641–5.

    PubMed  CAS  Google Scholar 

  48. Eilber F, Eckardt J, Rosen G, Forscher C, Selch M, Fu YS. Improved complete response rate with neoadjuvant chemotherapy and radiation for high grade extremity soft tissue sarcoma. Proc Annu Meet Am Soc Clin Oncol 1994; 13: A1645.

    Google Scholar 

  49. Casper ES, Gaynor JJ, Harrison LB, Panicek DM, Hajdu SI, Brennan MF. Preoperative and postoperative adjuvant combination chemotherapy for adults with high grade soft tissue sarcoma. Cancer 1994; 73: 1644–51.

    PubMed  CAS  Google Scholar 

  50. Eilber F, Eckardt J, Rosen G, Forscher C, Selch M, Fu YS. Preoperative therapy for soft tissue sarcomas. Hematol Oncol Clin North Am 1995; 9: 817–23.

    PubMed  CAS  Google Scholar 

  51. Goorin A, Schwartzentruber D, Gieser P, et al. No evidence for improved event free survival with presurgical chemotherapy for non-metastatic extremity osteogenic sarcoma: preliminary results of a randomized pediatric oncology group trial 8651, an update. Med Pediatr Oncol 1996; 27: 263.

    Google Scholar 

  52. Henshaw RM, Shmookler BM, Malawer MM. Histologic response of high-grade soft tissue sarcomas to induction chemotherapy. Paper presented at: Connective Tissue Oncology Society Annual Meeting; October 1999; Arlington, VA.

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Correspondence to Robert Mikael Henshaw MD.

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Henshaw, R.M., Priebat, D.A., Perry, D.J. et al. Survival After Induction Chemotherapy and Surgical Resection for High-Grade Soft Tissue Sarcoma. Is Radiation Necessary?. Ann Surg Oncol 8, 484–495 (2001). https://doi.org/10.1007/s10434-001-0484-8

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