Association of local recurrence with subsequent survival in extremity soft tissue sarcoma.

PURPOSE The aim of this study was to analyze local recurrence in a large cohort of prospectively followed patients with primary extremity soft tissue sarcoma. In particular, we analyzed the correlation of local recurrence with subsequent metastasis and disease-specific survival. PATIENTS AND METHODS Patients who underwent treatment for primary extremity soft tissue sarcoma from July 1982 through July 1995 at Memorial Sloan-Kettering Cancer Center were the subject of this study. Local recurrence, distant metastasis, and disease-specific survival were used as end points of the study. The influence of local recurrence on subsequent distant metastasis and disease-specific survival were examined using the Cox proportional hazards model. RESULTS We treated 911 patients, of whom 297 (33%) developed recurrent disease. Local recurrence occurred in 116 patients (13%), metastasis in 167 (18%), and synchronous local recurrence and metastasis in 13 (2%). Of 116 patients who developed local recurrence, 38 subsequently developed metastasis and 34 died of disease. Metastasis after local recurrence was predicted in patients with initial high-grade (P = .005; risk = 3.5) or deep (P = .02; risk = 2.9) tumors. Tumor mortality after local recurrence was predicted in patients with initial high-grade (P = .007; risk = 3.7) or large (> 5 cm; P = .01; risk = 3.2) primary tumors. DISCUSSION These findings suggest that there is a strong association of local recurrence with the development of subsequent metastasis and tumor mortality, and that local recurrence is a poor prognostic factor. It would seem prudent to consider patients who develop local recurrence and have high-grade tumors as being at high risk for systemic disease and therefore eligible for investigational adjuvant systemic therapy.

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Long-term results of a prospective randomized trial of adjuvant brachytherapy in soft tissue sarcoma.

Journal of Clinical Oncology ◽

10.1200/jco.1996.14.3.859 ◽

1996 ◽

Vol 14 (3) ◽

pp. 859-868 ◽

Cited By ~ 676

Author(s):

P W Pisters ◽

L B Harrison ◽

D H Leung ◽

J M Woodruff ◽

E S Casper ◽

...

Keyword(s):

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Local Control ◽

Distant Metastasis ◽

Soft Tissue Sarcomas ◽

Complete Resection ◽

High Grade ◽

Disease Specific Survival ◽

Recurrence Rates ◽

Disease Specific

PURPOSE This trial was performed to evaluate the impact of adjuvant brachytherapy on local and systemic recurrence rates in patients with soft tissue sarcoma. PATIENTS AND METHODS In a single-institution prospective randomized trial, 164 patients were randomized intraoperatively to receive either adjuvant brachytherapy (BRT) or no further therapy (no BRT) after complete resection of soft tissue sarcomas of the extremity or superficial trunk. The adjuvant radiation was administered by iridium-192 implant, which delivered 42 to 45 Gy over 4 to 6 days. The two study groups had comparable distributions of patient and tumor factors, including age, sex, tumor site, tumor size, and histologic type and grade. RESULTS With a median follow-up time of 76 months, the 5-year actuarial local control rates were 82% and 69% in the BRT and no BRT groups (P = .04), respectively. Patients with high-grade lesions had local control rates of 89% (BRT) and 66% (no BRT) (P = .0025). BRT had no impact on local control in patients with low-grade lesions (P = .49). The 5-year freedom-from-distant-recurrence rates were 83% and 76% in the BRT and no BRT groups (P = .60), respectively. Analysis by histologic grade did not demonstrate an impact of BRT on the development of distant metastasis, despite the improvement in local control noted in patients with high-grade lesions. The 5-year disease-specific survival rates for the BRT and no BRT groups were 84% and 81% (P = .65), respectively, with no impact of BRT regardless of tumor grade. CONCLUSION Adjuvant brachytherapy improves local control after complete resection of soft tissue sarcomas. This improvement in local control is limited to patients with high-grade histopathology. The reduction in local recurrence in patients with high-grade lesions is not associated with a significant reduction in distant metastasis or improvement in disease-specific survival.

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Localized Extremity Soft Tissue Sarcoma: Improved Knowledge With Unchanged Survival Over Time

Journal of Clinical Oncology ◽

10.1200/jco.2003.02.026 ◽

2003 ◽

Vol 21 (14) ◽

pp. 2719-2725 ◽

Cited By ~ 213

Author(s):

Jürgen Weitz ◽

Christina R. Antonescu ◽

Murray F. Brennan

Keyword(s):

Risk Factors ◽

Prognostic Factors ◽

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Current Therapy ◽

Disease Specific Survival ◽

Actuarial Survival ◽

Extremity Soft Tissue Sarcoma ◽

Risk Patients ◽

Disease Specific

Purpose: The objective of this study was to define whether survival of patients with extremity soft tissue sarcoma (STS), stratified for known risk factors, has improved over the last 20 years. Patients and Methods: From January 1982 to December 2001, 1,706 patients with primary and recurrent STS of the extremities were treated at our institution and were prospectively followed. From this cohort, we selected 1,261 patients who underwent complete macroscopic resection and had one of the following histopathologies: fibrosarcoma, liposarcoma, leiomyosarcoma, malignant fibrous histiocytoma, or synovial sarcoma. Median follow-up was 55 months. Patient, tumor, and treatment factors were analyzed as prognostic factors. Results: The 5-year disease-specific actuarial survival was 79% (78% for patients treated from 1982 to 1986, 79% for patients treated from 1986 to 1991, 79% for patients treated from 1992 to 1996, and 85% for patients treated from 1997 to 2001; P = not significant). For high-risk patients (high-grade, > 10 cm, deep tumors; n = 247), 5-year disease-specific survival was 51% (50% for patients treated from 1982 to 1986, 45% for patients treated from 1986 to 1991, 52% for patients treated from 1992 to 1996, and 61% for patients treated from 1997 to 2001; P = not significant). Tumor depth, size, grade, microscopic margin status, patient age, presentation status (primary tumor versus local recurrence), location (proximal versus distal), and certain histopathologic subtypes were significant prognostic factors for disease-specific survival on multivariate analysis; however, time period of treatment was not. Conclusion: Prognosis of patients with extremity STS, stratified for known risk factors, has not improved over the last 20 years, indicating that current therapy has reached the limits of efficacy.

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Refinement of clinicopathologic staging for localized soft tissue sarcoma of the extremity: a study of 423 adults.

Journal of Clinical Oncology ◽

10.1200/jco.1992.10.8.1317 ◽

1992 ◽

Vol 10 (8) ◽

pp. 1317-1329 ◽

Cited By ~ 195

Author(s):

J J Gaynor ◽

C C Tan ◽

E S Casper ◽

C F Collin ◽

C Friedrich ◽

...

Keyword(s):

Soft Tissue ◽

Local Recurrence ◽

Soft Tissue Sarcoma ◽

Distant Metastasis ◽

Prognostic Value ◽

Cox Model ◽

Metastatic Spread ◽

Outcome Variable ◽

High Grade ◽

Clinicopathologic Staging

PURPOSE The prognostic value of factors used in clinicopathologic staging of localized soft tissue sarcoma (STS) of the extremity were analyzed comprehensively. PATIENTS AND METHODS Four hundred twenty-three patients with STS that was confined to the extremity were admitted to Memorial Sloan-Kettering Cancer Center from 1968 to 1978. Cox models for the hazards rates of tumor mortality, development of a distant metastasis, strictly local recurrence, and postmetastasis survival were developed. Tests of changes in the prognostic value of the important variables over time were performed, as well as an analysis of the effect of a local recurrence on the hazard rate of distant metastasis. RESULTS Three unfavorable characteristics contained independent prognostic value for the rates of distant metastasis and tumor mortality: high grade (P less than .00001), deep location (P less than .0002), and size greater than or equal to 5 cm (P less than .007). Their Cox model coefficients did not differ significantly (P greater than or equal to .65); thus, a staging scheme based on the risk of ever developing a distant metastasis would assign equal prognostic weights to grade, depth, and size. The tumor grade effect during the initial 18 months was much larger in magnitude than those for depth and size, and its effect disappeared beyond that time (P = .0003). Thus, a staging scheme based on the risk of early metastatic spread would assign a distinctly larger prognostic weight to grade and lesser but equal weights to depth and size. There was no local recurrence effect on the rate of distant metastasis in the high-risk group (high grade, deep, and greater than or equal to 5 cm; P = .75), but there was a significant association among the remaining groups combined (P = .0039). The magnitude of this association actually increased according to the number of favorable characteristics presented (P = .0024). CONCLUSIONS The refinement of clinicopathologic staging may depend on the choice of outcome variable: ultimate prognosis versus early metastatic spread. Additionally, the observed local recurrence effect may be explained by a tendency for some patients to acquire one or more unfavorable risk factors at the time of local recurrence.

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