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Prognostic Index for Extremity Soft Tissue Sarcomas With Isolated Local Recurrence

From the Royal Marsden Hospital, Fulham Road, London, United Kingdom.

Correspondence: Address correspondence and reprint requests to: Ramesh Chandran Ramanathan, University of Pittsburgh Medical Center, C-800, PUH, 200 Lothrop Street, Pittsburgh, PA 15213; Fax: 412-647-4710; E-mail: ramanathanrc{at}msx.upmc.edu

	ABSTRACT

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Background: Local recurrence occurs in 10% to 20% of patients with extremity soft tissue sarcomas despite optimal treatment. The association of local recurrence with subsequent survival is controversial and conflicting. There is a need for a staging system to predict outcome in this subset of patients and also to plan optimal treatment, including adjuvant systemic therapy.

Methods: Data collected from 110 patients with locally recurrent extremity soft tissue sarcomas were studied. The influence of clinical and pathologic factors on local recurrence, distant metastasis, and disease-specific survival were analyzed by univariate and multivariate techniques.

Results: Of the 110 patients who presented with local recurrence, 92 had an isolated local recurrence and 18 had prior or concomitant distant metastases. The 5-year disease-specific survival for all patients was 63% and for those with isolated local recurrence, it was 69%. Histologic grade, malignant fibrous histiocytoma histology, pathologic margins, previous local recurrence, and prior radiotherapy were independent prognostic factors for subsequent local recurrence. Tumor size, histologic grade, and time to local recurrence were independent prognostic factors for distant metastasis and disease-specific survival. A prognostic index was calculated by assigning a score of 1 to 3 for each of the three independent prognostic factors for survival and added to give the prognostic index for each patient. As the prognostic index increased from 3 to 9, there was a progressive increase in the hazard ratios and a corresponding deterioration in survival. The patients were then categorized into three prognostic groups based on the hazard ratios for disease specific survival. The differences in the survival curves were highly statistically significant (P < .0001).

Conclusions: Tumor size, histologic grade, and time to local recurrence are the primary determinants of distant metastases and survival in locally recurrent extremity soft tissue sarcomas. The impact of local recurrence on survival varies considerably. The nature of the local recurrence, rather than its presence per se, is a more useful guide to prognosis. We propose a simple staging system based on size, grade, and time to recurrence that correlates extremely well with prognosis and may serve as a guide to make therapeutic decisions in patients with locally recurrent extremity soft tissue sarcomas.

Key Words: Soft tissue sarcoma • Local recurrence • Staging • Prognostic factors

	INTRODUCTION

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Soft tissue sarcomas are a heterogeneous group of malignant neoplasms, which arise from extraskeletal connective tissues of the body and are grouped together because of similarities in clinical presentation, pathologic appearance, and biologic behavior. They are rare tumors, accounting for approximately 1% of adult malignancies¹ with an annual age adjusted incidence of 2 per 100,000.²

Local recurrence occurs in 10% to 20% of patients with primary extremity soft tissue sarcomas, despite optimal multimodality treatment.^3–5 The association between local recurrence and subsequent metastases and survival is controversial.⁶ Several retrospective studies have addressed these issues with differing conclusions. Some authors consider local recurrence to be a grave prognostic sign,^3,7–14 whereas others argue that the appearance of systemic disease is independent of local recurrence and that local disease can usually be salvaged without impairment of survival.^15–22

A large proportion of patients present to tertiary referral centers with local recurrence after primary surgery performed elsewhere, and information such as size or grade of the primary tumor may not be available.²³ The therapeutic options for these patients still remain controversial, partly because of disagreement over the role of local recurrence in the etiology of subsequent metastases. There is a need for a staging system to predict outcome in this subset of patients and also to plan optimal treatment, including adjuvant systemic therapy.

This study was undertaken in a series of locally recurrent extremity soft tissue sarcomas treated in a single institution by a uniform treatment policy during a recent time period. The aim of the study was to evaluate prognostic factors for locally recurrent extremity sarcomas and to develop a simple staging system that will predict outcome and assist in planning optimal treatment. We performed univariate and multivariate analysis to evaluate the effect of various clinicopathologic factors on the end points of local recurrence, metastasis-free survival and disease-specific survival using prospectively collected data.

	PATIENTS AND METHODS

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During the period from November 1989 to October 1995, 677 patients with soft tissue sarcoma were referred for definitive treatment to the Sarcoma Unit at the Royal Marsden Hospital. Of these, there were 110 patients who presented with local recurrence after having received treatment for the primary soft tissue sarcoma elsewhere. Eighteen patients had prior or concomitant distant metastatic disease, and the remaining 92 patients with isolated locally recurrent extremity sarcomas were used to study prognostic factors. Each patient was registered at presentation, and clinical, pathologic, treatment, and outcome details were prospectively entered into a database.

All the patients underwent a CT scan of the chest for staging at presentation. Treatment was by wide surgical excision where possible and every effort was taken to preserve at least one innervated muscle in a compartment (functional compartmental resection)²⁴ to improve functional outcome. Adjuvant postoperative radiotherapy was given to patients with high-grade tumors or where only a marginal resection has been performed, i.e., where the tumor has been exposed during removal or if histologic margins are positive after definitive resection. Preoperative radiotherapy was used when there was clinical or radiologic doubt about resectability. The decision to treat the patient with adjuvant radiotherapy was also dependent on whether the patient had received prior radiotherapy and, if so, the dose and fields of radiation.

The following clinical and pathologic factors—sex, age, anatomic site (distal vs. proximal extremity and upper vs. lower extremity), history of prior local recurrence, history of previous radiotherapy, time to local recurrence, histopathologic subtype, histologic grade, microscopic surgical margins, and tumor size—were evaluated by univariate and multivariate analysis for their influence on the end points of local recurrence, metastasis-free survival, and disease-specific survival. Treatment-related factors were not included, as treatment decisions are made based on the presence or absence of risk factors and their inclusion along with clinicopathologic factors as covariates in a multivariate analysis could lead to misleading results.

Tumors at the level of or distal to the knee or elbow were classified as distal tumors. Tumor size was defined as the maximum diameter of the tumor measured at pathologic analysis of the specimen or as measured from the pretreatment CT scan in the minority of patients not treated by primary surgery. A single pathologist reported the pathologies of all the tumors. Tumors were divided into three grades (low, intermediate, and high) based on an assessment of tumor differentiation, mitotic activity and amount of necrosis.²⁵ The time to local recurrence was defined as the period in months from the date of definitive surgery for the primary tumor (performed elsewhere) to the date of diagnosis of the local recurrence. In those who have had multiple previous local recurrences, the time from the date of surgery for the last local recurrence to the date of diagnosis of the current local recurrence was taken as the time to local recurrence.

Statistical Analysis
Tabulated data were analyzed using the ² test unless one or both of the parameters were ordinal in which case the Mann-Whitney test or Spearman rank correlation was used. Life tables were calculated using the product limit method of Kaplan and Meier²⁶ and were compared using the log rank test.²⁷ Multivariate analysis of survival data was undertaken using Cox’s regression.²⁸ All the factors that were significant (P < .05) on univariate analysis were tested in the multivariate model. Factors were selected for multivariate analysis using forward stepwise selection. The single most significant factor (on univariate analysis) was first entered into the model. This was followed by the next most significant factor (once allowance had been made for the first factor) and so on. Analysis was performed to end points beyond the first recurrence, and patients experiencing one form of recurrence were not censored from the analysis of other forms of recurrence.

	RESULTS

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Patient Characteristics
The median age of the study group (110 patients) was 56 years with a range of 6–94 years. There were 54 males and 56 females (M:F = 1:1). The most common histologic types were liposarcoma (23%), leiomyosarcoma (22%), malignant fibrous histiocytoma (15%), synovial sarcoma (14%), and malignant peripheral nerve sheath tumors (8%). Other histologic types (fibrosarcoma, clear cell sarcoma, epithelioid sarcoma, angiosarcoma, malignant hemangiopericytoma, soft tissue chondrosarcoma, alveolar soft part sarcoma, rhabdomyosarcoma, and dermatofibrosarcoma protuberans) constituted 17 cases (16%) and 2 cases (2%) were unclassified (sarcoma NOS). The distribution of patients by tumor size and histologic grade is shown in Fig. 1. The median tumor size was 4.5 cm with a range of 1–17 cm (mean, 5.38 cm). Of the 110 patients with local recurrence, 7 patients had a prior history of distant metastases, 11 patients presented with concurrent distant metastases, and 92 patients had an isolated local recurrence. Seventy-two patients presented to us with their first local recurrence, whereas 38 patients had a history of prior local recurrence. Nineteen patients had 1 previous local recurrence, 9 patients had 2, 4 patients had 3, 2 patients had 4, 3 patients had 5, and 1 patient had 13 previous local recurrences.

View larger version (36K): [in this window] [in a new window]   FIG. 1. Distribution of the patients according to size and grade. The numbers on the bars refer to the number of patients in each group.

Outcome
The 5-year disease-specific survival for all 110 patients was 63% and the 5-year metastases-free survival was 60%. Of the 99 patients who were considered locally disease free at the end of treatment, 30 patients developed a subsequent local recurrence (30.3%). Fourteen patients developed local recurrence only, 16 patients developed distant metastasis only and 16 patients developed both local recurrence and distant metastasis. Patients with prior or concurrent distant metastases had a poor survival compared with the patients with isolated local recurrence (Fig. 2). The 5-year disease-specific survival for the 92 patients with isolated local recurrence was 69%, and the metastases free survival was 67%. Patients with local recurrence and concurrent distant metastases had a median survival of 11.7 months. The median follow-up of survivors is 42 months.

View larger version (15K): [in this window] [in a new window]   FIG. 2. Survival curves of patients with isolated local recurrence, prior distant metastases, and concurrent distant metastases.

Distant Metastasis
Large tumor size, intermediate and high histologic grades, shorter time to local recurrence, positive microscopic surgical margins, and leiomyosarcoma histology were adverse prognostic factors whereas liposarcoma histology was a favorable prognostic factor for distant metastasis on univariate analyses. Tumor size, histologic grade, time to local recurrence, and leiomyosarcoma histology were independent prognostic factors on multivariate analysis.

Disease-Specific Survival
Large tumor size, intermediate and high histologic grades, shorter time to local recurrence, positive microscopic surgical margins, and leiomyosarcoma histology were adverse prognostic factors on univariate analysis. Patients with liposarcoma histology had a better survival when compared with the rest but the difference was not statistically significant (P = .06). On multivariate analysis, tumor size, histologic grade, and time to local recurrence were the only independent prognostic factors for disease-specific survival.

Tumor size, histologic grade, and time to local recurrence were the most significant independent adverse factors for distant metastasis and were the only determinants of tumor related mortality. There was a progressive decrease in disease-specific survival with increase in tumor size (Fig. 3) and with an increase in histologic grade (Fig. 4). Patients were grouped into three groups based on the time to local recurrence: < 6 months, 6 to 36 months, and > 36 months. There was a progressive increase in survival with an increase in the time to local recurrence (Fig. 5).

View larger version (14K): [in this window] [in a new window]   FIG. 3. Effect of tumor size on disease-specific survival.

View larger version (15K): [in this window] [in a new window]   FIG. 4. Effect of histologic grade on disease-specific survival.

View larger version (16K): [in this window] [in a new window]   FIG. 5. Effect of "time to local recurrence" on disease-specific survival.

View larger version (18K): [in this window] [in a new window]   FIG. 6. Survival curves according to the proposed staging system for locally recurrent extremity soft tissue sarcomas.

	DISCUSSION

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A large proportion of patients with soft tissue sarcoma, up to 40% in some series, present to tertiary referral centers with local recurrence after primary surgery performed elsewhere.²³ The therapeutic options for patients with locally recurrent sarcomas remain controversial. Some authors advocate amputation once local failure has occurred,^8,31,32 whereas others propose an aggressive multimodality approach with wide local excision combined with radiation and chemotherapy to preserve a functional extremity.³³ The controversy over treatment is partly due to the disagreement over the role of local recurrence in the etiology of subsequent distant metastases. Local recurrence has been considered by some to be an ominous prognostic sign with an increased risk of subsequent metastatic disease and death,^3,7–14 whereas others believe that the appearance of systemic disease is independent of local recurrence and that local recurrence does not adversely affect survival.^15–22 The latter view is supported by the results of two prospective randomized trials that evaluated treatment approaches for soft tissue sarcomas, which showed that better local control does not translate into improvement in survival.^34,35

Local recurrence predisposes to further local recurrence. The local recurrence rate in patients who presented with local recurrence after primary treatment elsewhere (30.3%) was higher than the local recurrence rate of patients treated for primary sarcomas at our institute (16%).³⁶ Presentation with local recurrence has been shown by other studies to be a prognostic factor for further local recurrence.^8,22,37–39 Histologic grade, positive microscopic margins, and MFH histology were risk factors for local recurrence as has been reported by others^{9,20,21,37,38,40–42}. In addition, we found that among patients with local recurrence, those with one or more prior local recurrences were more prone to develop further local recurrence. Also, patients who have developed a local recurrence, despite prior radiotherapy are at a higher risk of developing further local recurrence.

Local recurrence without distant metastases should be treated aggressively because fairly high 5-year survival rates can be achieved, which are similar to those achieved after treatment of primary sarcomas. In our study, the 5-year survival of all patients presenting with local recurrence after primary surgery elsewhere was 63% and the 5-year survival of those with an isolated local recurrence was 69%. The 5-year survival of patients with local recurrence without concurrent metastases has ranged from 65% to 76% in previously reported studies.^20,33,43 In a survey by the American College of Surgeons, the 5-year survival after salvage therapy of isolated local recurrence was 61%.⁴⁴ Several studies have also shown that there is no difference in survival between patients who presented with primary sarcoma and those presenting initially with local recurrence.^38,45

The prognostic factors for distant metastases and survival in our study were tumor size, histologic grade, and time to local recurrence. Tumor size and histologic grade are the two most important prognostic factors for survival that have been consistently identified in primary soft tissue sarcomas.³⁶ In a series of 93 patients with locally recurrent sarcomas, tumor size and grade of the recurrent tumor had a significant impact on survival.⁴³ The time to local recurrence is measure of the biologic aggressiveness of the tumor. Cantin et al., in a study of 784 soft tissue sarcomas, suggested a relationship between timing of the recurrence and prognosis.⁸ They found that 69% of patients developing recurrences within the first 2 years died, whereas only 31% of patients with later recurrences died. In a series of 134 locally recurrent sarcomas, Choong et al. found that the size of the local recurrence and the time to local recurrence were significant risk factors for subsequent metastases and survival.⁴⁶ The median survival for patients who developed local recurrence within 1 year was 14 months and for those who developed local recurrence after 1 year was over 5 years. They also calculated a growth rate index (GRI) by dividing the size of the local recurrence (centimeters) by the time to local recurrence (months). The 2-year metastases-free survival of patients with a low GRI (<.4) was 80% and that for patients with a high GRI (>.4) was 30%. In a study of 240 soft tissue sarcomas from Finland, patients who developed local recurrence within 1 year from diagnosis had a significantly poorer survival.¹⁶ Ruka et al. studied the prognostic impact of tumor size/symptom duration ratio as an indicator of the growth rate of soft tissue sarcomas and found that the ratio was significantly related to survival for both primary and recurrent tumors.⁴⁷ Also, the length of time between treatment of the primary tumor and diagnosis of metastases has been shown to be an important prognostic factor for survival after pulmonary metastatectomy.⁴⁸

Local recurrence may be an indication of either inadequate primary treatment or of a highly malignant tumor with aggressive local growth. Local recurrence is a marker of risk and not a direct cause of distant metastases. Therefore, the prognostic significance of local recurrence may vary depending on the biology of the tumor. This variation explains the controversy in the literature regarding the association between local recurrence and distant metastases or survival. We have shown that the prognostic impact of the local recurrence can be determined based on the nature of the local recurrence. The size and histologic grade of the recurrent tumor along with the time to local recurrence are factors that reflect the biological nature of the tumor and, hence, determine the prognosis. Patients with a small low-grade recurrent tumor that develops more than 3 years after the primary treatment have an excellent prognosis with a 5-year survival of > 95%. On the other hand, a patient with a large high-grade recurrent tumor recurring within 6 months has a worse prognosis with a 5-year survival < 20%. Evans has suggested the importance of distinguishing two patterns of locally recurrent disease. Local recurrence after limited surgery, which is labeled "local persistence," is often innocent, whereas local recurrence after radical surgery is a grave sign.⁴⁹ He also suggested that the prognosis depends on the size and grade of the recurrent tumor and that survival is compromised only when the local recurrence exceeds the size of the original tumor. His observations are consistent with our results and conclusions.

Locally recurrent tumors without concurrent metastases are a selected subset with a good prognosis and should be analyzed separate from primary sarcomas.⁵⁰ They may represent tumors with less biologic potential to metastasize, as they have not metastasized detectably between the time from the treatment of the primary tumor and the diagnosis of local recurrence. There is a need for a staging system for patients presenting with isolated local recurrence that can reliably differentiate good and poor survival groups so that rational treatment can then be offered based on their prognosis. There is only one study in the literature that has attempted to devise a staging system for locally recurrent soft tissue sarcomas.⁴² Choong et al.⁴² constructed a staging system by using a combination of primary tumor necrosis and growth rate index (GRI) calculated by dividing size of the recurrent tumor by the time to local recurrence. Combination of the two factors created four prognostic groups: (1) no necrosis, GRI < .4; (2) no necrosis, GRI > .4; (3) necrosis, GRI < .4; (4) necrosis, GRI > .4, with a 2-year metastases-free survival of 94%, 79%, 61%, and 6%, respectively. Interestingly, they have used the same three prognostic factors that were identified to impact on distant metastases and survival in our study, namely, tumor size, histologic grade (as reflected by presence or absence of necrosis), and time to local recurrence. However, they have used information such as necrosis of the primary tumor, which may not be available for patients presenting with local recurrence after primary surgery elsewhere. Also, it seems that a GRI of .4 was arbitrarily chosen as a cut-off point, as it resulted in equal numbers of patients in the two groups in their study.⁴⁶ Tumor size and time to local recurrence are continuous variables, and stratifying soft tissue sarcomas using a single cut-off point for these factors does not provide sufficient prognostic categorization.

In contrast, our staging system is simple and relies only on information about the recurrent tumor that is readily available. Tumor size, histologic grade, and time to local recurrence are each assigned a score of 1 to 3, which are then added to give the prognostic index for each patient. The prognostic index accurately predicts the prognosis for each patient with worsening survival as the index goes from 3 to 9. The patients can be staged into three prognostic groups based on the index. Patients in the low-risk group (Index of 3, 4, or 5) have an excellent prognosis (>90% 5-year survival) and treatment should be aimed at preserving a functional extremity. Those in the intermediate-risk group (Index 6 or 7) have a 5-year survival of around 50% and would be candidates for adjuvant chemotherapy trials. Patients in the high-risk group (Index 8 or 9) have a predicted 5-year survival of <20%, and some of them may qualify for only palliative treatment. Patients presenting with locally recurrent tumors along with concomitant distant metastases will form the fourth prognostic group with the worst prognosis (median survival, 11.7 months). In view of the moderate sample size, the results are suggestive rather than conclusive and the proposed prognostic index needs to be validated in a larger study.

In conclusion, tumor size, histologic grade, and time to local recurrence are the primary determinants of distant metastases and survival in locally recurrent extremity soft tissue sarcomas. The impact of local recurrence on survival varies considerably. The nature of the local recurrence, rather than its presence per se, is a more useful guide to prognosis. We propose a simple staging system based on size, grade, and time to recurrence that correlates extremely well with prognosis and may serve as a guide to make therapeutic decisions in patients with locally recurrent extremity soft tissue sarcomas.

	Acknowledgments

 
Supported by a grant from the Sarcoma Unit Research Fund at the Royal Marsden Hospital.

Received for publication May 24, 2000. Accepted for publication November 8, 2000.

	REFERENCES

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION REFERENCES

 

1. Enzinger FM, Weiss SW. Soft Tissue Tumors. 3rd ed. St. Louis, MO: Mosby-Year Book Inc., 1995 1–16.
2. Cutler SJ, Young JL. Third National Cancer Survey. Incidence data. NCI Monograph No. 41, NIH No. 75-787, NCI, Bethesda, MD, 1975.
3. Lewis JJ, Leung D, Heslin M, Woodruff JM, Brennan MF. Association of local recurrence with subsequent survival in extremity soft tissue sarcoma. J Clin Oncol 1997; 15: 646–52.[Abstract/Free Full Text]
4. Karakousis CP, Driscoll DL. Treatment and local control of primary extremity soft tissue sarcomas. J Surg Oncol 1999; 71: 155–61.[CrossRef][Medline]
5. Brennen MF, Casper ES, Harrison LB, Shiu MH, Gaynor J, Hajdu SI. The role of multimodality therapy in soft tissue sarcoma. Ann Surg 1991; 214: 328–36.[Medline]
6. Barr LC, Stotter AT, A’Hern RP. Influence of local recurrence on survival: a controversy reviewed from the perspective of soft tissue sarcoma. Br J Surg 1991; 78: 648–50.[Medline]
7. Lieberman Z, Ackerman LV. Principles in management of soft tissue sarcomas. A clinical and pathological review of one hundred cases. Surgery 1954; 35: 350–65.
8. Cantin J, McNeer GP, Chu F, Booher RJ. The problem of local recurrence after treatment of soft tissue sarcomas. Ann Surg 1968; 168: 47–53.[Medline]
9. Markhede G, Angervall L, Stener B. A multivariate analysis of the prognosis after surgical treatment of malignant soft tissue tumors. Cancer 1982; 49: 1721–1733.[CrossRef][Medline]
10. Owens JC, Shiu MH, Smith R, Hajdu SI. Soft tissue sarcomas of the hand and foot. Cancer 1985; 55: 2010–8.[CrossRef][Medline]
11. Collin C, Godbold J, Hajdu S, Brennan M. Localized extremity soft tissue sarcoma. An analysis of factors affecting survival. J Clin Oncol 1987; 5: 601–12.[Abstract/Free Full Text]
12. Rooser B, Attewell R, Berg NO, Rydholm A. Survival in soft tissue sarcoma. Prognostic variables identified by multivariate analysis. Acta Orthop Scand 1987; 58: 516–22.[Medline]
13. Emrich LJ, Ruka W, Driscoll DL, Karakousis CP. The effect of local recurrence on survival time in adult high grade soft tissue sarcomas. J Clin Epidemiol 1989; 42: 105–10.[CrossRef][Medline]
14. Stotter AT, A’Hern RP, Fisher C, Mott AF, Fallowfield ME, Westbury G. The influence of local recurrence of extremity soft tissue sarcoma on metastasis and survival. Cancer 1990; 65: 1119–29.[CrossRef][Medline]
15. Abbas JS, Holyoke ED, Moore R, Karakousis CP. The surgical treatment and outcome of soft tissue sarcoma. Arch Surg 1981; 116: 765–9.[Abstract]
16. Rantakokko V, Ekfor TO. Sarcomas of the soft tissue in the extremities and limb girdles. Analysis of 240 cases diagnosed in Finland in 1960–1969. Acta Chir Scand 1979; 145: 385–94.
17. Potter DA, Kinsella T, Glatstein E, et al. High grade soft tissue sarcomas of the extremities. Cancer 1986; 58: 190–205.[CrossRef][Medline]
18. Rooser B, Gustafson P, Rydholm A. Is there no influence of local control on the rate of metastases in high-grade soft tissue sarcoma? Cancer 1990; 65: 1727–1729.[CrossRef][Medline]
19. Gustafson P, Rooser B, Rydholm A. Is local recurrence of minor importance for metastases in soft tissue sarcoma?. Cancer 1991; 67: 2083–6.[CrossRef][Medline]
20. Singer S, Antman K, Corson JM, Eberlein TJ. Long-term salvageability for patients with locally recurrent soft tissue sarcomas. Arch Surg 1992; 127: 548–54.[Abstract]
21. 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: 165–73.[Medline]
22. Ueda T, Yoshikawa H, Mori S, et al. Influence of local recurrence on the prognosis of soft tissue sarcomas. J Bone Joint Surg (Br) 1997; 79: 553–7.
23. Serpell JW, Ball ABS, Robinson MH, Fryatt I, Fisher C, Thomas JM. Factors influencing local recurrence and survival in patients with soft tissue sarcoma of the upper limb. Br J Surg 1991; 78: 1368–72.[Medline]
24. Pitcher ME, Thomas JM. Functional compartmental resection for soft tissue sarcomas. Eur J Surg Oncol 1994; 20: 441–5.[Medline]
25. Trojani M, Contesso G, Coindre JM, et al. Soft tissue sarcomas of adults. Study of pathological prognostic variables and definition of histopathological grading system. Int J Cancer 1984; 33: 37–42.[Medline]
26. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Soc 1958; 53: 457–481.
27. Mantle N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 1966; 50: 163–170.[Medline]
28. Cox DR. Regression models and life tables (with discussion). J R Stat Soc B 1972; 34: 187–220.
29. Martin RG, Butler JJ, Albores-Saavedra. Soft tissue tumors: surgical treatment and results. In: Tumors of Bone and Soft Tissue. Chicago: Year Book Medical Publishers, 1965.
30. Rougraff B. Surgery for local control of soft tissue sarcoma. In: The Diagnosis and Management of Soft Tissue Sarcomas of the Extremities in the Adult. Curr Prob Cancer 1999; 23: 23–38.
31. Shiu MH, Castro EB, Hajdu SI, Fortner JG. Surgical treatment of 297 soft tissue sarcomas of the lower extremity. Ann Surg 1975; 182: 597–602.[Medline]
32. Gerner RG, Moore GE, Pickren JW. Soft tissue sarcomas. Ann Surg 1975; 181: 803–8.[Medline]
33. Guiliano AE, Eilber FR, Morton DL. The management of locally recurrent soft tissue sarcoma. Ann Surg 1982; 196: 87–91.[Medline]
34. Rosenberg SA, Tepper J, Glatstein E, et al. The treatment of soft tissue sarcomas of the extremities. Prospective randomized evaluations of (1) limb sparing surgery plus radiation compared with amputation and (2) the role of adjuvant chemotherapy. Ann Surg 1983; 196: 305–15.
35. Brennan MF, Hilaris B, Shiu MH, Lane J, Magill G, Friedrich C, Hajdu SI. Local recurrence in adult soft tissue sarcoma. A randomized trial of brachytherapy. Arch Surg 1987; 122: 1289–93.[Abstract]
36. Ramanathan RC, A’Hern RP, Fisher C, Thomas JM. Modified staging system for extremity soft tissue sarcomas. Ann Surg Oncol 1999; 6: 57–69.[Abstract]
37. Pisters PWT, Leung DHY, Woodruff J, Shi W, Brennan MF. Analysis of prognostic factors in 1041 patients with localized soft tissue sarcomas of the extremities. J Clin Oncol 1996; 14: 1679–89.[Abstract/Free Full Text]
38. Collin CF, Friedrich C, Godbold J, Hajdu S, Brennan M. Prognostic factors for local recurrence and survival in patients with localized extremity soft tissue sarcoma. Semin Surg Oncol 1988; 4: 30–7.[Medline]
39. Trovik CS, Bauer HCF. Local recurrence of soft tissue sarcoma a risk factor for late metastases. 379 patients followed for 0.5–20 years. Acta Orthop Scand 1994; 65: 553–8.[Medline]
40. Herbert SH, Corn BW, Solin LJ, et al. Limb-preserving treatment for soft tissue sarcomas of the extremities. The significance of surgical margins. Cancer 1993; 72: 1230–8.[CrossRef][Medline]
41. Heslin MJ, Woodruff J, Brennan MF. Prognostic significance of a positive microscopic margin in high risk extremity soft tissue sarcoma. Implications for management. J Clin Oncol 1996; 14: 473–8.[Abstract/Free Full Text]
42. Choong PFM, Gustafson P, Willen H, et al. Prognosis following locally recurrent soft tissue sarcoma. A staging system based on primary and recurrent tumor characteristics. Int J Cancer 1995; 60: 33–7.[Medline]
43. Karakousis CP, Proimakis C, Rao U, Velez AF, Driscoll DL. Local recurrence and survival in soft tissue sarcomas. Ann Surg Oncol 1996; 3: 255–60.[Abstract]
44. Lawrence W, Donegan WL, Natarajan N, Mettlin C, Beart R, Winchester D. Adult soft tissue sarcomas. A pattern of care survey of the American College of Surgeons. Ann Surg 1987; 205: 349–59.[Medline]
45. Wilson RB, Crowe PJ, Fisher R, Hook C, Donnellan MJ. Extremity soft tissue sarcoma: factors predictive of local recurrence and survival. Aust N Z J Surg 1999; 69: 344–9.[CrossRef][Medline]
46. Choong PFM, Gustafson P, Rydholm A. Size and timing of local recurrence predicts metastasis in soft tissue sarcoma. Growth rate index retrospectively analyzed in 134 patients. Acta Orthop Scand 1995; 66: 147–52.[Medline]
47. Ruka W, Emrich LJ, Driscoll DL, Karakousis CP. Tumor size/symptom duration ratio as a prognostic factor in patients with high grade soft tissue sarcomas. Eur J Cancer Clin Oncol 1988; 24: 1583–8.[CrossRef][Medline]
48. Roth JA, Putnam JBJr, Wesley MN, Rosenberg SA. Differing determinants of prognosis following resection of pulmonary metastases from osteogenic and soft tissue sarcoma patients. Cancer 1985; 55: 1361–6.[CrossRef][Medline]
49. Evans RA. Soft tissue sarcoma: the enigma of local recurrence. J Surg Oncol 1993; 53: 88–91.[Medline]
50. Gustafson P, Dreinhofer KE, Rydholm A. Metastasis-free survival after local recurrence of soft tissue sarcoma. J Bone Joint Surg (Br) 1993; 75: 658–60.

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