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(Chest. 2005;127:902-908.)
© 2005 American College of Chest Physicians

Soft-Tissue Sarcomas of the Chest Wall*

Prognostic Factors

Jefferson Luiz Gross, MD, PhD; Riad Naim Younes, MD, PhD; Fabio José Haddad, MD, PhD; Daniel Deheinzelin, MD, PhD; Clovis Antonio Lopes Pinto, MD, PhD and Marcelo Leite Vieira Costa, MD

* From the Departments of Thoracic Surgery (Drs. Gross, Younes, Haddad, Deheinzelin, and Vieira Costa) and Pathology (Dr. Lopes Pinto), Hospital do Cancer A. C. Camargo, Sao Paulo, Brazil.

Correspondence to: Jefferson Luiz Gross, MD, PhD, Rua Prof Antonio Prudente, 211, Liberdade, Sao Paulo, Brazil; e-mail: jefluizgross{at}yahoo.com.br


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Objective: To evaluate factors that are predictive of outcome for patients with chest wall soft-tissue sarcomas.

Patients and methods: A retrospective review of 55 surgically treated patients, from March 1964 to October 1996.

Results: The median age of the patients was 47.5 years (age range, 15 to 76.3 years), and 56.4% were men. The most common presenting symptom was chest wall mass in 29 patients (52.7%). The median symptom duration was 12 months. Tumor size ranged from 1 to 26 cm (median size, 9.7 cm). The most common histologic type of tumor was fibrosarcoma (52.7%). Twenty-three sarcomas (41.8%) were high-grade, and 32 sarcomas (52.8%) were low-grade. Of the 55 patients, 27 (49.1%) had previously been treated elsewhere (surgical resection, 23 patients; radiation therapy and surgery, 3 patients; chemoradiation therapy, 1 patient). Previously treated patients presented either with residual disease (10 cases) or recurrence of disease (17 cases). All 55 patients underwent surgical resection, 15 patients (27.3%) were treated by neoadjuvant chemoradiation therapy, and 2 patients were treated by adjuvant radiotherapy. Wide surgical resection was performed in 45 patients (81.8%), and marginal resection was performed in 10 patients (18.2%). The median follow-up time was 51.9 months. Local recurrence of disease developed in 6 patients, and metastases developed in 10 patients. The overall survival rates at 5 and 10 years were 87.3% and 79.3%, respectively. Tumor size < 5 cm and low histologic grade were determinants of better survival at univariate analyses. Multivariate analyses disclosed only histologic grade as an independent predictor for the risk of death. Disease-free survival rates at 5 and 10 years were 75.3% and 64.2%, respectively. Tumor size < 5 cm, performance of wide surgical resection, and low histologic grade were determinants of a better disease-free survival rate. Independent prognostic factors for disease-free survival were histologic grade and type of surgical resection

Conclusion: The clinical behavior of chest wall soft-tissue sarcomas is similar to that of extremity sarcomas. Thoracic wall soft-tissue sarcomas are best controlled by wide surgical resection.

Key Words: prognosis • sarcoma • surgery • thoracic wall


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Primary soft-tissue sarcoma of the chest wall is a rare disease. Of the 8,000 new cases of soft-tissue sarcomas that are diagnosed annually in the United States, < 10% arise in the chest wall.12 Most series in the literature are small and usually extend over several decades, with a large variety of therapeutic approaches. On the other hand, in most of these series, soft-tissue sarcomas of the chest wall were usually analyzed together with bony and cartilaginous chest wall tumors, neoplasms metastatic to the chest wall, and soft-tissue sarcomas of other primary sites.345

Furthermore, some authors include chest wall soft-tissue sarcoma in an ill-defined anatomic site that is referred to as the trunk. There is no agreement about which structures are encompassed in the trunk definition. Some authors include sarcomas arising from the thoracic and abdominal wall,6 others include visceral and retroperitoneal tumors,7 while others do not define exactly8 which anatomic sites should be included as the trunk. The importance of such differences relies on the fact that the primary location of soft-tissue sarcomas is a determinant of prognosis. Patients with tumors arising from the retroperitoneum and the head and neck characteristically present with poorer survival rates than those with extremity tumors.910

Extremity soft-tissue sarcomas, the most frequent primary tumor site, have well-determined prognostic factors, such as anatomic location, histologic grade, and tumor size. These data are usually extrapolated to predict the clinical outcome of patients with tumors in other primary sites. Only a few studies1112 have analyzed the prognostic factors for patients with primary soft-tissue sarcoma of the chest wall. Because of their rarity, prognostic factors for thoracic wall soft-tissue sarcomas are usually studied together with those for primary extremity tumors, but it is not clear whether tumors at these different sites exhibit the same clinical behavior.

The main purpose of the present study was to evaluate the prognostic importance of clinical and pathologic variables in a series of 55 patients with primary soft-tissue sarcomas that are confined exclusively to the chest wall, who underwent surgical resection in a single institution.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
From March 1964 to October 1996, 75 patients in whom primary soft-tissue sarcoma of the chest wall was diagnosed were admitted to the Hospital do Cancer A. C. Camargo in Sao Paulo, Brazil. These patients were identified by a retrospective review of all histopathologic results that were on file in the Department of Pathology at our institution. Clinical data were obtained by a chart review of these patients.

A single pathologist, who was blinded to the clinical outcome of the patients, reviewed all pathologic material. Tumor specimens were obtained either from surgical resection or from biopsy in patients who had undergone neoadjuvant treatment. Histologic classification was based on sections stained with hematoxylin-eosin. The histologic subtype was determined according the recommendations of the World Health Organization.

Statistical Analysis
The method of Kaplan and Meier13 was used to determine actuarial survival times. Survival times from the date of hospital admission to the last follow-up or death were used for the estimation. Disease-free survival was defined as the interval between the date of admission at our center and the date of the diagnosis of a first recurrence. Differences in survival were determined by log-rank analysis. The following variables were analyzed for prognostic purposes: sex; age (divided into patients < 47 years of age and patients ≥ 47 years of age); symptoms at presentation (pain vs no pain); duration of symptoms (< 1 year vs ≥ 1 year); tumor size (< 5 cm vs ≥ 5 cm); tumor location (anterior vs posterior vs lateral); status of the tumor on admission at our hospital (intact vs only biopsy vs treated elsewhere); status of the tumor after previous treatment (residual disease vs local recurrence); type of surgical resection performed (wide excision vs marginal resection); type of treatment (surgical resection alone vs combined modalities); histologic subtype (fibrosarcoma vs other types); and histologic grade (high vs low). Multivariate analysis of these variables was performed by the Cox proportional hazard model,14 including the variables of prognostic value that had been identified by univariate analysis. Cox multiple regression was used to identify variables that independently influence the risk of tumor recurrence (local and systemic).

All statistical analyses were performed using a statistical software package (SPSS, version 8.0; SPSS; Chicago, IL). A p value of ≤ 0.05 was defined as significant.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Twenty of the 75 patients who initially had been identified were excluded from this study due to the following causes: 8 patients had not undergone surgical treatment (refused surgical resection, 4 patients; had progression to metastases after neoadjuvant treatment, 2 patients; considered unresectable at hospital admission, 2 patients); 6 patients were < 15 years old; 3 patients had metastases at diagnosis; and 3 patients did not receive any treatment at our institution. A database was created by retrospective chart review, and the variables were examined concerning the remaining 55 patients.

The patient population ranged in age from 15 to 76.3 years (median age, 47.5 years). There were 31 male patients (56.4%) and 24 female patients (43.6%). Presenting symptoms included chest wall mass in 29 patients (52.7%), pain associated with a mass in 18 patients (32.7%), pain alone in 4 patients (7.3%), and dyspnea in only one patient (1.8%). Three patients (5.5%) were asymptomatic. Information about the duration of symptoms was obtained in 52 patients, ranged in duration from 1 to 144 months (median duration, 12 months). Tumor location in the chest wall was as follows: posterior, 32 tumors (58.2%); anterior, 17 tumors (30.9%); and lateral, 6 tumors (10.9%). The size of the tumor was determined in 48 patients (87.3%) and ranged in size from 1 to 26.5 cm (median size, 9.7 cm).

Before hospital admission, 20 patients (36.4%) did not receive any treatment, while 8 patients (14.5%) had undergone only a biopsy of the tumor, and 27 patients (49.1%) had previously been treated elsewhere. The previous treatment was surgical resection alone in 23 patients, radiation therapy and surgery in 3 patients, and neoadjuvant chemoradiation followed by surgical resection in 1 patient. Previously treated patients presented either with residual disease (10 patients) or disease recurrence (17 patients). At our institution, all 55 patients underwent surgical resection of the chest wall tumor, and of these, 38 patients (69.1%) underwent surgical resection alone, 15 patients (27.3%) were treated by neoadjuvant chemoradiation, and two patients (3.6%) were treated by surgical resection followed by adjuvant radiotherapy.

The types of surgical resection were classified as follows: wide excision (ie, adequate surgical margins defined by the surgeon), 45 patients (81.8%); and marginal resection (ie, inadequate margins defined by the surgeon), 10 patients (18.2%). As this was a retrospective study, it was difficult to objectively quantify the size of the surgical margins based only on the surgical report of every chart. The status of the microscopic margins was not available in every chart.

The most common tumor subtype was fibrosarcoma (52.7%), followed by liposarcoma (14.5%). Table 1 shows the distribution of patients according to histologic subtypes. All sarcomas were classified as low-grade or high-grade on the basis of the number of mitoses, and the amount of necrosis and cellular differentiation. Tumors were classified as high-grade in 23 patients (41.8%) and low-grade in 32 patients (58.2%).


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  		Table 1.. Distribution of Chest Wall Soft-Tissue Sarcomas According to Histologic Subtypes

 
After treatment, all patients were routinely followed up in our institution. The median time of follow-up was 51.4 months, and ranged from 19 days to 340 months. Disease recurrence was observed in 16 patients (29.1%), and of these, local recurrence occurred in 6 patients and distant metastases occurred in 10 patients. The lungs were the most common site of metastasis (eight patients) followed by bone (two patients). At the time of the chart review, the status of the 55 patients included in this study was as follows: alive without disease, 28 patients (50.9%); alive with disease, 7 patients (12.7%); dead of cancer, 7 patients (12.7%); dead due to other causes, 2 patients (3.6%); and unavailable for follow-up, 11 patients (20%).

Overall Survival Rates
The overall 5-year and 10-year survival rates were 87.3% and 79.4%, respectively. Tables 2-4 , show the influence of different variables on the 5-year overall survival rate. Only tumor size significantly correlated with prognosis (Fig 1 , top, A). Even though patients with local disease recurrence after receiving the initial treatment had a lower overall survival rate (79.3% at 5 years) than patients with residual disease (100% at 5 years), this difference did not reach statistical significance (p = 0.08).


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  		Table 2.. Actuarial Overall and Disease-Free Survival Rates According to Clinical Variables*

 

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  		Table 3.. Actuarial Overall and Disease-Free Survival Rates According to Therapeutic Variables*

 

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  		Table 4.. Actuarial Overall and Disease-Free Survival Rates According to Pathologic Variables*

 


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  		Figure 1.. Overall survival. Top, A: overall survival time according to tumor size (p = 0.02). Bottom, B: overall survival time by histologic grade (p < 0.01).

 
Patients who underwent marginal resection had a lower 5-year overall survival rate (67.5%) than patients who were treated with wide surgical resection (92.1%), but this difference failed to reach statistical significance (p = 0.18). Patients who received neoadjuvant and/or adjuvant treatment had similar overall survival rates, compared to patients treated with surgery alone (Table 3).

Histologic type was not related to clinical outcome. However, patients with high-grade soft-tissue sarcomas of the chest wall had a worse overall 5-year survival rate (69.2%) than did those with low-grade sarcomas (100%; p < 0.01), as shown in Figure 1, bottom, B. Multivariate analysis disclosed only histologic grade as being an independent predictor for the risk of death (Table 5 ).


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  		Table 5.. Multivariate Analyses of Overall Survival

 
Disease-Free Survival
The disease-free survival rates estimated at 5 years and 10 years were 75.3% and 64.2%, respectively. Table 2 shows the influence of different clinical variables on disease-free survival. Patients with tumors < 5 cm in size had a better disease-free survival rate than did those with tumors > 5 cm in size (p = 0.05). Patients who had undergone wide surgical resection had a better 5-year disease-free survival rate (84.7%) than patients who had been treated by marginal surgical resection (40%; p < 0.01) [Table 3, Fig 2 ]. As observed for the overall survival rate, patients with low-grade soft-tissue sarcoma of the chest wall had better 5-year disease-free survival (86%) than did patients with high-grade tumors (59.9%; p = 0.05) [Table 4]. Other clinical, therapeutic, and histologic variables did not significantly influence disease-free survival. Multivariate analysis disclosed that only histologic grade and type of surgical resection were independent prognosticators for disease-free survival (Table 6 ).



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  		Figure 2.. Disease-free survival time by type of surgical resection (p < 0.01).

 

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  		Table 6.. Multivariate Analyses of Disease-Free Survival

 
Risk of Recurrence
Patients who had undergone marginal resection had a 3.3 times higher risk of recurrence compared to patients who had undergone wide surgical resection (95% confidence interval [CI], 0.88 to 12.37; p = 0.07). The risk of distant metastases was related to histologic grade. Patients with high-grade soft-tissue sarcomas had a 6.5 times higher risk of developing metastases when compared to patients with low-grade tumors (95% CI, 1.37 to 30.55; p = 0.02).


   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
Primary soft-tissue sarcomas of the chest wall are uncommon. Due to the limited experience accumulated by single institutions with this neoplasm, there are few series of patients described in the literature. Most published studies678 of soft-tissue sarcomas have categorized tumors arising in the chest wall or abdominal wall, and sometimes in the viscera as truncal sarcomas, without clearly defining the meaning of trunk. The extremities are the most common primary site of soft-tissue sarcomas, and the prognostic factors for this kind of disease are well-defined. Size, histologic grade, location (deep or superficial), local recurrence at presentation, histologic subtypes, and status of microscopic margins have been identified as determinants of prognosis in patients with soft-tissue sarcomas of the extremities.1516 Few studies1112 of prognostic factors have suggested that soft-tissue sarcomas of the chest wall and primary extremity sarcomas have similar prognoses. However, there are no studies comparing the clinical behavior of these different primary sites of soft-tissue sarcomas.

The present study reported the experience of a single institution with these uncommon tumors over a 32-year period, and it is the second largest reported series of soft-tissue sarcomas of the chest wall. There are only two previous studies in the medical literature that have exclusively considered patients with primary soft-tissue sarcomas of the chest wall. Greager et al11 analyzed 49 patients with soft-tissue sarcomas of the thoracic wall who had been treated by the Division of Surgical Oncology at the University of Illinois, but the authors did not report the period of patient accrual. The largest series of patients exclusively considered who had soft-tissue sarcomas of the chest wall was reported by Gordon et al12 in 1991. The authors reviewed their 40-year experience with 149 patients with soft-tissue sarcoma of the thoracic wall who had undergone surgical resection at Memorial Sloan-Kettering Cancer Center in New York. This study included patients with desmoid tumors (32 of 149 patients), which some authors do not classify histologically as sarcomas. On the other hand, desmoid tumors have a high rate of local recurrence and should be treated as low-grade sarcomas.17 In our analysis, we excluded patients with desmoid tumors.

The median age of 47.5 years and the predominance of male over female patients in our study are similar to the data observed in other series of chest wall soft-tissue sarcomas and in also series of sarcomas localized in different anatomic sites.61215 Despite the fact that other authors included patients of any age,12 in the present study we decided to exclude patients < 15 years of age due to the distinct clinical behavior of soft-tissue sarcomas in children.18

Similarly to previous studies, the present study showed a painless mass as the most common initial presentation of sarcomas arising in the thoracic wall. In our patients, the median duration of symptoms was 12 months, which was similar to the time observed by Gordon and colleagues12 and is longer than that for patients with tumors in other sites. The tumor diameter in the majority of our patients was > 9 cm. We think that the long duration of symptoms and the large sizes of the tumors in our series can be explained by the fact that the majority of these patients had low-grade and painless tumors, which tend to grow slowly.

Our 5-year overall survival rate (87.3%) was greater than that observed by Gordon et al (66%).12 The disease-free survival rates at 5 years and 10 years in the present study (75.3% and 64.2%, respectively) was greater than those observed by Greager and coworkers (68% and 51%, respectively).11 We think that this better result can be explained again by the fact that there were more patients with low-grade tumors in our series.

There was a significant difference in overall survival rate based on tumor size and histologic grade. Patients with a tumor diameter of < 5 cm and a low histologic grade had a better overall survival rate after univariate analysis. Both variables also appear as the most important prognosticators in most series of extremity soft-tissue sarcomas.1516

Surgical resection is the treatment of choice for soft-tissue sarcomas. However, in our patient population the type of surgical resection (wide or marginal) did not significantly influence the overall survival rate. Wide surgical resection was disclosed as a significant prognostic factor in the present study. However, we do not know the microscopic results of the surgical margins in all cases. Since this is the best definition of wide- excision surgery, prospective studies using the microscopic status of margins should be performed.

Neoadjuvant therapy (ie, chemotherapy and radiation therapy) or adjuvant therapies (ie, radiotherapy) did not have an impact on the overall survival rate, compared to the performance of surgical resection alone. Patients treated before admission to our center had similar overall survival rate when compared to patients who had been admitted to our center without previous treatment. However, among previously treated patients, those with recurrent disease had a worse overall survival rate than did patients with residual disease at hospital admission, but this difference did not reach statistical significance. Walsh et al19 observed similar results in their series. Although the type of surgical resection did not influence the overall survival rate, it showed importance in determining recurrence-free survival. This data suggest that adequate surgical resection is the most important therapeutic approach for patients with chest wall soft-tissue sarcomas, as shown by other authors as well.351720 Thoracectomy is a safe surgical procedure, with low morbidity and mortality rates,21 and should be performed on all patients with soft-tissue sarcomas of thoracic wall.

We observed that the type of surgery and histologic grade were able to determine the risk of recurrence in an independent manner. The type of surgical resection was related to local recurrence, with inadequate surgical resection increasing the risk of local recurrence by 3.3 times. Histologic grade was related to a higher risk for metastases, with patients having tumors of high histologic grade having a 6.5 times higher risk of metastases developing. As such, it is conceivable that patients with high-grade soft-tissue sarcomas of the chest wall should be evaluated for neoadjuvant or adjuvant systemic treatment to reduce the risk of metastatic recurrence and death.

The present study suggests that the clinical behavior of chest wall soft-tissue sarcomas was similar to that of tumors arising in the extremities, where histologic grade is one of the most important determinants of the overall survival rate. Moreover, thoracic wall soft-tissue sarcomas are best controlled by wide surgical resection, which is similar to the control of extremity tumors. The majority of patients with chest wall soft-tissue sarcomas are amenable to wide surgical resection with negative margins, as are patients with sarcomas arising in the extremities. Probably, the worse survival rate observed in patients with retroperitoneal, head-and-neck, and visceral soft-tissue sarcomas is related to the difficulty in reaching adequate margins during surgical resection.


   Footnotes
 
Abbreviation: CI = confidence interval

Received for publication March 1, 2004. Accepted for publication August 27, 2004.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

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