Radiation Therapy Oncology Group (RTOG) 9514: A phase II study of neoadjuvant chemotherapy (CT) and radiation therapy (RT) in the management of high risk (HR), high grade (HG) soft tissue sarcomas (STS) of the extremities and body wall

Reviewer: Neha Vapiwala, MD
Last Modified: June 1, 2003

Presenter: W. G. Kraybill
Presenter's Affiliation: RTOG
Type of Session: Scientific


    The preliminary data from this RTOG phase II trial of neoadjuvant chemotherapy and radiation in high risk soft tissue sarcoma patients was first presented at ASCO a few years ago. This presentation is an update of that data including analysis of all pts with longer follow-up to evaluate toxicity, complication rates, and efficacy rates

Materials and Methods

  • 66 pts enrolled with primary high grade soft tissue sarcomas of the extremities (81%) or body wall (19%), measuring > 8 cm in diameter
  • 64 pts analyzed for toxicity, response rate, complication rate and treatment failure - "failure" defined as persistent local disease, disease relapse or surgical amputation
  • Protocol specified the following treatment regimen: 1) preoperative modified MAID chemotherapy (Mesna, Adriamycin, Ifosfamide, DTIC) x 3 cycles 2) radiation of 44 Gy given in split courses of 22 Gy between chemo cycles; boost of 16 Gy for postive margins postoperatively 3) surgical resection 4) postoperative modified MAID chemotherapy x 3 cycles


  • 3-yr overall survival of 75%
  • 3-yr distant disease-free survival of 64.4%
  • 3-yr disease-free survival of 55.2%
  • 14 deaths, 11 were sarcoma-specific and 1 was treatment-related
  • 3-yr treatment failure rate of 20%
  • Failure rates by surgical outcome: - 52 pts with clear margins --> 3 (6%) failed - 3 pts with involved margins --> 2 failed - 5 pts with amputation --> all 5 failed - 4 pts did not get surgery --> 3 failed, 1 had complete response after preoperative chemotherapy and radiation alone
  • Protocol compliance rates: - 79% got 3 cycles preoperative chemo - 89% got radiation as per protocol - 61% got 3 cycles postoperative chemo
  • Combined grade 4 toxicity rate of 88% - hematologic grade 4 = 80% - nonhematologic grade 4 = 23%
  • Delayed wound healing seen in 31%, but serious or severe degree seen only in 11%, as rest were minimal delays

Author's Conclusions

  • The use of neoadjuvant chemotherapy and radiation with additional postoperative chemotherapy for large, high grade soft tissue sarcomas appears to be feasible in this multi-institutional study.
  • The regimen has considerable toxicity but is still possible with careful assessment and management of any treatment complications.
  • In light of the overall and distant disease-free survival rates seen here, there appears to be efficacy of this aggressive combined modality approach in high risk pts.

Clinical/Scientific Implications

    The treatment approach in high risk soft tissue sarcoma patients is an evolving one. This study shows updated survival data suggesting a benefit with neoadjuvant chemotherapy and radiation as well as postoperative consolidation chemotherapy in these patients. The toxicity profile of such an approach must be weighed against the potential benefit and likelihood of downstaging prior to surgery on an individualized basis. Treatment failure in these high risk patients is likely a multifactorial process rather than a shortcoming of any single modality. A separate analysis of those patients completing the entire treatment as per protocol might help to shed some light on this matter.

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