Preoperative Chemotherapy for Soft-tissue Sarcomas of the Extremities

Pezzi, Christopher M.; Pollock, Raphael E.; Evans, Harry L.; Lorigan, James G.; Pezzi, Thomas A.; Benjamin, Robert S.; Romsdahl, Marvin M.

doi:10.1097/00000658-199004000-00015

Cited by 129 publications

(56 citation statements)

References 9 publications

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“…However, it has not been determined if radiographic response correlates with survival. 1,3 In the current study, we hypothesized that any decrease in tumor volume may favorably affect local …”

Section: Discussionmentioning

confidence: 97%

“…Finally, tumor response to preoperative chemotherapy may provide prognostic information. 1 Response to NeoCT is usually monitored using serial cross-sectional imaging. Although the pathologic response to NeoCT is a predictor of local recurrence and survival, 2 this information is available only after surgical resection.…”

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confidence: 99%

“…Although preoperative patient management decisions are based on the radiographic response to therapy, there is no consensus among studies that this response correlates with survival. 1,3 Therefore, in this study, we tested the hypothesis that radiographic response to NeoCT predicts improved local tumor control and survival rates.…”

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confidence: 99%

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Radiographic response to neoadjuvant chemotherapy is a predictor of local control and survival in soft tissue sarcomas

Meric

Hess

Varma

et al. 2002

Cancer

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109

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BACKGROUNDDownstaging of large soft tissue sarcomas can be accomplished by the use of neoadjuvant chemotherapy (NeoCT). The authors tested the hypothesis that radiographic response to NeoCT predicts improved local control and survival.METHODSThe authors reviewed the medical records of 65 patients with Stage II or III soft tissue sarcoma (42 extremity, 23 retroperitoneal) who were treated with doxorubicin or ifosfamide‐based NeoCT from January 1991 to December 1996. Radiographic response and impact on surgical therapy were determined retrospectively by comparing imaging studies obtained before and after chemotherapy.RESULTSThe radiographic responses observed were partial response (PR; 22 patients [34%]); minor response (MR; 6 patients [9%]); stable disease (20 patients [31%]); and progressive disease (17 patients [26%]). Downstaging sufficient to decrease the scope of the operation occurred in 13% of the patients, 78% had no change, and 9% had disease progression sufficient to increase the scope of the operation. Patients having any radiographic response (PR or MR) had a higher margin‐negative resection rate, a better local recurrence‐free survival rate, and a better overall survival rate than did nonresponders.CONCLUSIONSThe NeoCT regimens used in this study resulted in tumor shrinkage sufficient to impact surgical therapy in a few patients. However, radiographic response predicted improved local control and overall survival rate. Cancer 2002;95:1120–6. © 2002 American Cancer Society.DOI 10.1002/cncr.10794

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Section: Discussionmentioning

confidence: 97%

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confidence: 99%

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Radiographic response to neoadjuvant chemotherapy is a predictor of local control and survival in soft tissue sarcomas

Meric

Hess

Varma

et al. 2002

Cancer

Self Cite

109

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“…44 Only a handful of reports have been published concerning the use of neoadjuvant chemotherapy for the treatment of soft tissue sarcomas. [45][46][47][48][49][50] The largest experience, as reported by Eilber, 50 included data on extremity sarcomas treated with five different preoperative protocols (all using adriamycin administered either intraarterially or intravenously, combined with preoperative radiation). Although their initial experience showed an increase in the local recurrence rate with reduced doses of radiation, their subsequent data showed further reductions in the local recurrence rate when cis platinum was added.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2001

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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 reresection 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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“…Few agents, such as doxorubicin, dacarbazine and ifosfamide, have been proven to be effective in the therapy of soft tissue sarcomas in general (4). However, these treatments have shown poor results and are rarely associated with significant improvements in overall survival (10). In disseminated disease, a response rate of 20-30% has been observed with doxorubicin, the most frequently used chemotherapeutic agent in the treatment of soft tissue sarcomas (1,11).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the safety and efficacy of TRAIL and taurolidine use on human fibrosarcoma xenografts in vivo

et al. 2016

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Abstract. Fibrosarcomas are rare malignant soft tissue tumours that exhibit a poor response to current therapeutic regimens. Previously, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and taurolidine were observed to induce apoptosis synergistically in HT1080 human fibrosarcoma cells in vitro. Consequently, the present study aimed to assess the safety and efficacy of TRAIL in combination with taurolidine on the local growth of fibrosarcoma xenografts in vivo. HT1080 fibrosarcoma cells were inoculated subcutaneously into both flanks of 49 athymic nude mice in order to establish tumour xenografts. TRAIL and taurolidine were applied intraperitoneally at various single and cumulative treatment doses. After 12 days, the experiment was terminated and surviving animals were euthanised. Tumour progression was determined during and following treatment. To assess the potential toxic effects of the two compounds, the organs (lung, liver, kidney and heart) of all animals were examined histologically. The results revealed that combined treatment with TRAIL and taurolidine significantly inhibited the growth of HT1080 xenografts, whereas untreated animals had steadily increasing tumours. The most effective combination was TRAIL at 2 µg per application (cumulative dose, 16 µg) and taurolidine at 30/15 mg per application (cumulative dose, 180 mg), reducing the mean size of implanted xenografts to 10.9 mm 2 following treatment (vs. 48.9 mm 2 in the control group; P=0.0100). Despite distinct tumour mass reduction, the rate of mortality was significantly increased in animals treated with TRAIL and taurolidine in a taurolidine dose-dependent manner; however, histological examinations of relevant organs revealed no evidence of systemic toxicity (mean survival time, 7.9 days in the treated groups vs. 12 days in the control group; P<0.0010). In summary, whilst the combination of TRAIL and taurolidine synergistically inhibited the growth of fibrosarcoma xenografts in vivo, it was also accompanied by significantly increased mortality rate. Thus, although taurolidine is assumed to be a compound with an acceptable toxicity profile, and therefore increasingly used in clinical trials, the current findings raise concerns with regard to its safety and therapeutic index, and indicate the requirement for further detailed toxicity tests.

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Preoperative Chemotherapy for Soft-tissue Sarcomas of the Extremities

Cited by 129 publications

References 9 publications

Radiographic response to neoadjuvant chemotherapy is a predictor of local control and survival in soft tissue sarcomas

Radiographic response to neoadjuvant chemotherapy is a predictor of local control and survival in soft tissue sarcomas

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

Evaluation of the safety and efficacy of TRAIL and taurolidine use on human fibrosarcoma xenografts in vivo

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