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© 2002 American Society for Clinical Oncology Clinical Features and Outcome of Initially Unresected Nonmetastatic Pediatric Nonrhabdomyosarcoma Soft Tissue SarcomaBy
Address reprint requests to Sheri L. Spunt, MD, Department of Hematology-Oncology, St Jude Children’s Research Hospital, 332 N Lauderdale St, Memphis, TN 38105-2794; email: sheri.spunt{at}stjude.org
PURPOSE: To describe the clinical features, response to therapy, and outcome of pediatric patients with initially unresected nonmetastatic nonrhabdomyosarcoma soft tissue sarcoma (NRSTS). PATIENTS AND METHODS: We retrospectively reviewed the presenting clinical features and tumor characteristics of all 40 pediatric patients with initially unresected nonmetastatic NRSTS who were seen at our institution between March 1962 and December 1996. A subset of 27 patients for whom complete treatment information was available was analyzed to determine whether response to therapy was associated with local disease control and event-free and overall survival. RESULTS: More than 70% of the 40 patients had tumors with high-risk features (tumor size > 5 cm, high grade, invasiveness). For the 27 patients included in the outcome analysis, 5-year event-free survival and survival estimates were 33% ± 9% and 56% ± 10%, respectively. Ten (37%) of these patients had a complete or partial response to neoadjuvant chemotherapy and/or radiotherapy, and only two of the 10 had residual tumor after surgery. Combined chemotherapy and radiotherapy seemed more effective than either modality alone in inducing a response, but the response to neoadjuvant therapy did not predict outcome. Most treatment failures were local, and postrelapse survival was poor (19% ± 10%). CONCLUSION: Initially unresected NRSTS constitutes a unique subgroup of pediatric sarcomas that commonly present with high-risk features and respond poorly to neoadjuvant therapy. Only about one third of patients treated with multimodal therapy remain disease-free, and local control is the major limiting factor in achieving cure. More effective risk-directed treatments are needed for this unique subgroup of patients.
Nonrhabdomyosarcoma soft tissue sarcomas (NRSTSs), which constitute approximately 4% of all childhood malignancies,1 differ greatly from rhabdomyosarcomas in their clinical features and response to therapy. Because pediatric NRSTSs tend to be relatively chemoresistant,2,3 surgical resection with or without radiotherapy is the mainstay of treatment for localized tumors. The role of adjuvant chemotherapy in improving survival remains controversial.4-6 With current therapies, more than 70% of children and adolescents with surgically resected nonmetastatic disease are expected to be cured.7,8 In contrast, fewer than 10% of patients with metastatic disease are expected to become long-term survivors.2,3 The outcome of patients with nonmetastatic NRSTS that is not resected at the time of diagnosis is largely unknown. In most adult series of nonretroperitoneal sarcomas, patients with "high-risk" nonmetastatic NRSTS are grouped with those who have metastatic disease, and thus their outcomes cannot be meaningfully interpreted. The two multi-institutional studies of pediatric NRSTS that have been reported treated patients with "resected" and "unresectable/metastatic" disease differently, perhaps because the extent of residual disease after initial surgery was observed to be prognostically important in pediatric rhabdomyosarcoma.9 Although one trial used neoadjuvant chemotherapy and radiotherapy for unresectable and metastatic pediatric NRSTS,2 the report did not describe in detail the clinical features, surgical outcomes, or pattern of treatment failure for the subset of patients with unresectable disease. In a retrospective analysis of children and adolescents with initially resected NRSTS treated at our institution, we found that high histologic grade, large tumor size, invasiveness, and positive microscopic margins were unfavorable prognostic features for event-free survival (EFS) and overall survival.8 Similar observations have been made in studies of adults with resected NRSTS.10,11 However, for patients whose tumors are not resected at the time of initial presentation, it is unknown whether outcome is entirely dependent on these known prognostic factors or whether the absence of initial resection is an independent predictor of poor outcome. Prior reports of pediatric NRSTS from our institution have not specifically addressed the prognostic importance of gross residual disease after initial surgery.12-14 We hypothesized that patients with unresected NRSTS constitute a unique subgroup whose clinical features and pattern of treatment failure differ from those of patients with resected or metastatic disease. We further hypothesized that the absence of complete resection at the time of initial presentation is an unfavorable prognostic factor that is independent of the other factors known to predict poor outcomes in patients with resected NRSTS. We therefore retrospectively reviewed our 34-year institutional experience to characterize the natural history of unresected NRSTS, to assess the contribution of neoadjuvant therapy and subsequent surgery to their cure, and to determine whether gross residual disease after initial surgery is an independent adverse prognostic factor.
Patients Between March 1962 and December 1996, 199 patients younger than 21 years of age who had a diagnosis of NRSTS were seen at St Jude Children’s Research Hospital. Forty patients had localized disease that was not resected at the time of initial diagnosis. Patients with desmoid tumor were excluded from this study.
Demographic data collected for this group of 40 patients included sex, race, age at the time of diagnosis, and duration of follow-up. The pathologic diagnosis was confirmed by one of the authors (D.A.H.) in the 33 cases for which diagnostic specimens were available. Histologic grade was determined by using the Pediatric Oncology Group grading system,15 which takes into account patient age and the histology, cellularity, necrosis, mitotic activity, and nuclear features of the tumor. Tumor characteristics that were tabulated included the primary tumor site (head and neck, extremity, trunk wall, intra-abdominal, intrathoracic), histologic pattern, size (
Response to treatment was analyzed in a group of 27 patients (68%). The remaining 13 patients were excluded from this analysis because records of their treatment before arrival at our institution were incomplete (n = 9), because no treatment was administered (n = 2), or because of previous treatment for another malignancy (n = 2). For this analysis, the details of any surgical procedures performed after neoadjuvant therapy and the chemotherapy and radiotherapy administered to the 27 patients were recorded. Tumor responses to neoadjuvant therapy were assessed. For patients who underwent definitive surgical resection of the primary tumor, the extent of residual tumor after surgery was recorded. The best response achieved by any treatment administered was also recorded for each patient. Responses to therapy were categorized as complete response (CR) (no evidence of residual tumor), partial response (PR) (
Statistical Methods The duration of local control was defined as the time interval between diagnosis and local or regional recurrence of disease. Competing risks for local treatment failure included distant recurrence and death before local recurrence. The duration of distant control was defined as the time interval between diagnosis and distant recurrence of disease. Competing risks for distant recurrence included local recurrence and death before distant recurrence. Patients who had simultaneous local and distant recurrence were considered to have local recurrence for the analysis of local control and distant recurrence for the analysis of distant control. The cumulative incidence of local and distant recurrence was estimated by the methods of Kalbfleisch and Prentice.18 Gray’s19 test was used to compare the cumulative incidence of local treatment failure among groups; no exact test was available. Demographic and updated outcome data were obtained for patients included in previously published series from our institution3,8 and were compared to data for the patients with unresected NRSTS.
Sixteen (40%) of the 40 patients were alive at the time of this analysis, with a median follow-up of 7.9 years (range, 4.5 to 26.3 years). Fifteen of the 16 survivors had been seen or contacted within the past year. The median age at the time of diagnosis of NRSTS for all 40 patients was 12.8 years (range, birth to 20.8 years), and three patients were younger than 1 year of age. There were 23 females (58%); 32 patients (80%) were white. The tumor characteristics of the 40 cases are listed in Table 1. The tumor most commonly arose in the extremities (13 patients [33%]) or the head and neck region (12 patients [30%]). The most common histologic diagnoses were malignant peripheral-nerve sheath tumor (11 patients [28%]), synovial sarcoma (eight patients [20%]), and sarcoma not otherwise specified (seven patients [18%]). Thirty-three patients (83%) had tumors more than 5 cm in greatest diameter, 32 (80%) had invasive tumors, and 29 (73%) had high-grade tumors. Three of the five patients who showed clinical evidence of lymph node involvement had biopsy confirmation of regional nodal metastasis. The majority of patients (21 [52%]) had AJCC stage III disease.
We found no statistically significant difference between the 27 patients whose responses to treatment were evaluated and the 13 patients excluded from this analysis, with respect to age at diagnosis of NRSTS (P = .3), race (P = .99), sex (P = .5), tumor invasiveness (P = .99), or AJCC stage (P = .06). The assessable patients had a lower proportion of extremity tumors (six of 27 [22%]) than the excluded patients (seven of 13 [54%]), although no statistically significant difference was seen (P = .072), and they had a significantly higher proportion of high-grade tumors (23 of 27 [85%]) than did the excluded patients (six of 13 [46%]) (P = .020). There was a trend toward a significant difference between the two groups in the size of the primary tumor (P = .074); 20 (74%) of the 27 evaluated patients and all 13 (100%) of the excluded patients had tumors more than 5 cm in greatest dimension.
Chemotherapy and Radiotherapy
Response to Neoadjuvant Therapy A favorable response to neoadjuvant therapy facilitated tumor resection (Table 2). Eight (80%) of the 10 patients who had a CR or PR and six (35%) of the 17 patients who had SD or PD after neoadjuvant therapy were free of disease after definitive surgery (P = .046). However, despite their superior surgical results, patients who had a CR or PR after neoadjuvant therapy did not have a lower risk of local or distant recurrence or a higher probability of survival. Their estimated 5-year cumulative incidence of local recurrence (40% ± 17%) was similar to that of patients who had SD or PD after neoadjuvant therapy (47% ± 13%) (P = .44). The estimated 5-year cumulative incidence of distant recurrence was similar in the two groups (20% ± 13% v 29% ± 12%, P = .67), as was the estimated probability of 5-year survival (50% ± 14% v 59% ± 12%, P = .77).
Results of Definitive Surgery Seventeen of the 27 assessable patients underwent a definitive surgical procedure (Table 2). No tumor was found in the resection specimens of two of these patients. Nine patients underwent gross total tumor resection; the microscopic margins were negative in seven cases and positive in two. Six patients underwent incomplete tumor resection; all had tumors arising in nonextremity sites (head and neck, n = 2; intra-abdominal, n = 2; and trunk wall, n = 2). Of the 10 patients who did not undergo surgery, three had a clinical CR to neoadjuvant therapy and six had PD. One patient with a high-grade hemangiopericytoma of the thigh had a PR after chemotherapy and radiotherapy, but the residual mass appeared fibrotic on diagnostic imaging. He received no further therapy and remains free of disease progression at the time of this report, 7.9 years after diagnosis. This patient and another adolescent who developed iliac nodal metastases after neoadjuvant chemotherapy were the only patients with extremity tumors who did not undergo surgery. Among the patients who underwent definitive surgery, the extent of tumor resection did not seem to influence the incidence of local or distant disease recurrence or the ultimate outcome. The estimated 5-year cumulative incidence of local recurrence was 33% in patients who had gross residual disease after surgery and 27% in those who had a gross total resection or had no evidence of tumor in the resected specimen (P = .66). Similarly, the estimated 5-year cumulative incidence of distant recurrence was comparable in patients who had gross disease after surgery (33%) and patients who had no gross residual disease (27%) (P = .70). The estimated probability of 5-year survival was slightly higher for patients who had no gross disease after surgery (82% ± 12% v 67% ± 17%), although no statistically significant difference was seen (P = .42).
Best Response to Therapy
Treatment Failure Among the 18 patients whose tumors recurred, 14 have died. One of the four survivors had a local recurrence, and three had isolated pulmonary metastases that were resected. At the time of this report, these four patients had survived 2.5, 3.5, 6.5, and 17.4 years after recurrence. The estimated probability of 5-year postrelapse survival was 19% ± 10% after tumor recurrence of any type, 9% ± 6% after local recurrence only, and 29% ± 17% after distant (or local and distant) recurrence. The only patient with an extremity tumor who died after local recurrence had developed regional nodal metastases at the time of the local recurrence. Ten patients died as the result of local tumor progression, two died of distant metastatic disease, and two (one with distant metastases and one with both local and distant disease) died of unknown causes.
Survival Estimates
Comparison of Resected and Unresected NRSTS As summarized in Table 4, NRSTS that was unresected at diagnosis was more likely to be large, high-grade, and invasive. Whereas resected NRSTS commonly involved the extremities and trunk wall, unresected NRSTS arose predominantly in the head and neck and in intra-abdominal/intrathoracic sites. Patients with initially unresected NRSTS seemed to have a prognosis intermediate to that of patients with localized resected disease (5-year survival estimate, 89% ± 2%) and patients with metastatic disease (5-year survival estimate, 15% ± 6%) (Fig 2).
The pattern of treatment failure and the likelihood of survival after disease recurrence also differed between the two groups. In patients with surgically resected disease, estimates of the 5-year cumulative incidence of local and distant failure were similar (13% ± 3% and 12% ± 3%), whereas local treatment failure predominated in patients with initially unresected disease (5-year cumulative incidence, 44% ± 10% v 26% ± 9%, respectively). Estimates of 5-year survival after recurrence were higher for patients with initially resected NRSTS than for patients with unresected tumors (55% ± 9% v 19% ± 10%, P = .021). Among the 18 patients whose tumors recurred, 14 have died. Most of the patients with initially unresected tumors who died (10 of 14 patients [71%]) had only local tumor progression at the time of death, whereas metastatic disease caused most deaths in patients with resected tumors (13 of 17 patients [76%]). The extent of resection at the time of diagnosis (resected v unresected) was an independently significant predictor of both EFS (P = .017) and survival (P = .028) after adjusting for tumor invasiveness, size, and histologic grade. Patients with unresected NRSTS were twice as likely to die as patients with resected tumors, when tumor grade, invasiveness, and size were controlled for (95% confidence interval for risk ratio, 1.1 to 4.0). However, six of the 17 patients with unresected tumors underwent gross total resection despite the presence of SD/PD after neoadjuvant therapy. Because it is possible that some or all of these six patients could have undergone resection at the time of initial diagnosis, we grouped these six with the patients whose tumors were resected at presentation and repeated the analysis. After adjusting for tumor grade, invasiveness, and size, we found that the patients with unresected tumors still had a significantly lower 5-year survival estimate (P = .022) and a marginally lower EFS estimate (P = .064). These findings demonstrate that the presenting features, natural history, and outcome of surgically resected and unresected NRSTS differ in several ways.
Our retrospective analysis of children and adolescents with localized, initially unresected NRSTS who were treated at a single institution demonstrates that approximately one half of these patients can be expected to survive 5 years after diagnosis. This finding confirms our hypothesis that patients with initially unresected NRSTS have a prognosis that is intermediate to that of patients with localized resected disease and that of patients with distant metastatic disease (Fig 2). Furthermore, our institutional experience clearly demonstrates that the presenting features and natural history of surgically resected and unresected NRSTS differ in several ways. NRSTS that is unresected at the time of diagnosis is more likely to be large, high-grade, and invasive. Whereas resected NRSTS commonly involves the extremities and trunk wall, unresected NRSTS arises predominantly at head and neck and intra-abdominal/intrathoracic sites. The pattern of treatment failure and the likelihood of survival after disease recurrence also seem to differ between the two groups. In patients with surgically resected disease, estimates of the 5-year cumulative incidence of local and distant failure were similar, whereas local treatment failure predominated in patients with initially unresected disease. We found that local recurrences in patients with unresected NRSTS were less common in the patients treated during the last decade of this study. The use of higher doses of radiotherapy for children with unresected tumors and improvements in the targeting and delivery of radiation therapy in the more recent treatment era likely explain this finding. However, the normal tissue tolerance of intra-abdominal, intrathoracic, and craniofacial structures continues to restrict the delivery of adequate radiotherapy in some patients, resulting in relatively high local recurrence rates among patients with unresected tumors. After local or distant disease recurrence, salvage therapy was effective for fewer than 20% of children with unresected disease but was effective for nearly 60% of children with surgically resected disease. Furthermore, mortality was associated with local tumor progression in patients with unresected tumors, whereas most deaths in patients with resected tumors were caused by metastatic disease. Taken together, these findings suggest that children with NRSTS that is initially unresected constitute a unique subgroup of patients for whom the development of risk-directed therapies is warranted. Because NRSTSs are generally not responsive to chemotherapy, the practice at our institution has been to proceed with surgical resection at the time of diagnosis, if gross tumor resection seems to be feasible. Thus, only 40 (24%) of our 169 patients with localized NRSTS diagnosed between 1962 and 1996 had gross residual disease after initial surgery. We acknowledge that the guidelines for surgical resection are arbitrary and depend in part on the technical expertise of the treating surgeon, so we cannot unequivocally state that all of the tumors in our study group would have been considered unresectable at other centers. Six (35%) of our 17 patients with SD or PD after neoadjuvant therapy subsequently underwent gross total tumor resection; therefore, some may not have had truly "unresectable" tumors at the time of initial diagnosis. However, it is also possible that neoadjuvant therapy induced sufficient tumor shrinkage in some of the patients with SD to allow surgical excision that would not otherwise have been feasible. It is worth noting that approximately three fourths of our patients whose tumors were not resected at the time of diagnosis had clinical features associated with an unfavorable outcome (high grade, large size, or invasiveness).8,10,11,20,21 Because this constellation of clinical features seems to be characteristic of unresectable tumors, the absence of these features should encourage an attempt at surgical resection. In this series, younger age was associated with a better clinical outcome. This finding has been confirmed in a larger series at our center,22 but the reasons for it remain largely unknown. Small tumor size, which is associated with more favorable outcomes, was not a more frequent finding in younger children. Although infantile hemangiopericytoma and infantile fibrosarcoma generally respond better to treatment than do histologically similar tumors in older children,23,24 both of the infantile tumors in this series recurred locally; this observation suggests that the association between age and histology does not explain the better outcome of our younger patients. Because young age at initial presentation is a favorable prognostic factor for other childhood sarcomas,25,26 we speculate that the tumors of younger patients may have favorable biologic features that have yet to be elucidated. With the advent of cDNA microarray and serial analysis of gene expression techniques, it may be possible to identify the genetic alterations associated with this favorable clinical behavior.27,28 Large tumor size (> 5 cm) was associated with unresected disease and with a lower likelihood of survival in our series. Surprisingly, although we previously found large tumor size to be associated with metastatic disease in surgically resected NRSTS,8 most tumor progression was local in the group of patients with initially unresected disease. Because many of these patients died after early local tumor recurrence, it is difficult to ascertain the likelihood of subsequent distant metastasis. Future improvements in local disease control for these patients may reveal a higher rate of distant recurrence. Although many other series of pediatric8,29 and adult10,11,20,21 NRSTS have shown an association between high histologic grade and lower survival estimates, we found no such association in this group of patients. The only other published series of children with unresected NRSTS noted a similar absence of association between histologic grade and outcome.2 Although the reasons for this finding are unclear, we speculate that the outcomes of children with unresected low- and high-grade tumors are comparable because these tumors tend to respond poorly to chemotherapy and radiotherapy and frequently arise in unfavorable sites that preclude complete surgical resection. In fact, two of the four assessable patients with low-grade tumors in our series experienced local disease recurrence, and both had tumors in unfavorable anatomic locations (paranasal sinus, intra-abdominal site). Our observation that histologic grade was not predictive of survival in unresected NRSTS must be interpreted with some caution, however, given the small number of patients in our series. Perhaps the most provocative finding of our study is that patients with unresected tumors fare more poorly than those whose tumors are resected at the time of initial diagnosis, even when the analysis is adjusted for other known high-risk features such as tumor grade, size, and invasiveness. This observation suggests that prognosis depends not only on the biologic and clinical features of the tumor but also on the surgical treatment undertaken at initial presentation. Although this conclusion must be considered tentative given the small and retrospective nature of our study, prospective clinical trials should include the extent of initial resection in multivariate analyses of outcome. If gross total surgical resection at the time of initial diagnosis is confirmed to be associated with better outcome, more aggressive surgical approaches may be warranted for patients with "unresectable" tumors. In our study group, the overall rates of response to neoadjuvant therapy and disease progression afterward were similar to those described in adult studies.30-33 Approximately two thirds of recurrences in our series were local and one third were distant, with a median time to progression of 10 months. In adults, however, metastatic recurrence is significantly more frequent than local progression.30,33 The high rate of local recurrence in our series reflects the fact that our patients’ tumors were considered to be unresectable at the time of diagnosis and the fact that most of their tumors arose in sites other than the extremities, where rates of local control are typically lower.10,11,34-37 The inclusion of patients with low-grade tumors10,38 and the large proportion of patients who died early of local disease progression are likely to account for the lower rate of metastatic disease seen in our series. We found that patients who responded to neoadjuvant therapy were more likely to be free of gross disease after definitive surgery but, surprisingly, were not more likely to have good clinical outcomes. Patients who had complete or partial responses to neoadjuvant therapy had rates of local recurrence, distant recurrence, and survival comparable to those of patients who had SD or PD after neoadjuvant therapy. Similar observations have been reported by Pisters et al.30 However, a more recent study at the same institution found that the response to preoperative therapy is well correlated with overall survival and the absence of local recurrence.31 The reasons for our findings are unclear. It is possible that radiographic measurement of response is misleading. Indeed, several previous studies of adults with NRSTS have documented a poor correlation between radiographic and pathologic evidence of response.30,32 It is possible that some of our patients who were classified as having SD on the basis of radiographic evaluation actually had a favorable pathologic response and thus had outcomes comparable to a CR or PR after neoadjuvant therapy. A recent analysis of adults with high-grade extremity NRSTS found that the pathologic response to neoadjuvant therapy was closely linked to outcome39; therefore, pathologic evaluation may be superior to radiographic evaluation in assessing the response to treatment. Finally, it is possible that the early response to therapy does not predict a patient’s ultimate outcome; we found that those who eventually achieved a CR or PR fared better than did those whose best response was SD or PD. These findings have important implications for treatment planning after neoadjuvant therapy, because patients who have a poor response to initial therapy may have a good likelihood of long-term survival with further aggressive treatment. Larger, prospective studies of the prognostic value of pathologic response may help resolve this issue. Although uniform neoadjuvant therapy was not used in our patient population, 55% of patients who were free of gross disease after definitive surgery had received both neoadjuvant chemotherapy and radiotherapy, whereas none of the patients who had residual gross disease had received both types of neoadjuvant therapy. Several studies in adults with NRSTS have also documented high rates of clinical and pathologic response to combined neoadjuvant therapy.40-42 A recent nonrandomized trial found that adults with stages II and III NRSTS who were treated with combined chemotherapy and radiotherapy had fewer local recurrences and a higher estimated probability of survival than did patients treated with chemotherapy alone.31 Unfortunately, however, preoperative radiotherapy is also associated with a greater risk of postoperative wound complications.43-46 Future trials should prospectively compare the efficacy of combined-modality neoadjuvant therapy with that of chemotherapy or radiotherapy alone. On the basis of our findings, we recommend that gross total resection be attempted at the time of diagnosis whenever it is feasible and does not cause significant disfigurement or disability. Specifically, patients with small, high-grade tumors and those with low-grade tumors are unlikely to benefit significantly from neoadjuvant therapy, and therefore aggressive efforts to remove the tumor at the time of initial presentation are warranted. Patients whose tumors are not amenable to resection and those with large, high-grade tumors who are at the greatest risk of distant metastasis should receive neoadjuvant therapy, preferably on clinical trials designed to identify effective treatment approaches. On the basis of our observation that patients who respond poorly to neoadjuvant therapy fare no worse than those who respond favorably, we strongly recommend an aggressive approach to local control, even if the response to initial therapy is not encouraging. Our findings must be interpreted with caution, given the retrospective nature of our study, the small number of patients evaluated, the extended study period, and the influence of improvements in surgery, radiotherapy, and chemotherapy. For example, a relatively small proportion of the patients in our series received ifosfamide, a drug that has improved response rates in some studies of adults with NRSTS.47,48 Therefore, the rates of response we observed may be lower than those that could be expected with modern ifosfamide-containing chemotherapy regimens. Further research is needed to confirm our findings. Optimally, prospective multi-institutional clinical trials for childhood NRSTS should be conducted with a uniform, risk-based therapy approach. The use of staging and histologic grading systems similar to those commonly used in adult NRSTS trials will facilitate the comparison of outcomes in pediatric and adult populations. Future pediatric trials should assess the relevance of the prognostic factors identified to date, seek more effective neoadjuvant therapies for children with high-risk disease, and assess the relationship between clinical and histopathologic indicators of treatment response and outcome.
Supported in part by Cancer Center grant no. CA 23099 and Cancer Center Support CORE grant no. P30 CA 21765 from the National Cancer Institute, and by the American Lebanese Syrian Associated Charities. The acknowledgment is available online at www.jco.org. We dedicate this work to the memory of the late Charles B. Pratt, MD,whose many contributions to the field of pediatric soft tissue sarcomas have advanced the care of children and adolescents with these tumors. We also thank St Jude staff members Pamela Hays (tumor registry), Sharon Naron, ELS (scientific editing), and the solid tumor data managers, and we thank Murray Brennan, MD, for his critical review of the article.
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Copyright © 2002 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
5 cm or > 5 cm), local invasiveness (yes or no), histopathologic grade (low [grades 1 and 2] or high [grade 3]), and regional lymph node status (positive or negative). All tumors arising in the abdomen, retroperitoneum, or pelvis were classified as intra-abdominal tumors, whereas tumors arising within the pleural cavity or mediastinum were classified as intrathoracic tumors. The stage of disease was determined according to the American Joint Committee on Cancer (AJCC) guidelines for soft tissue sarcomas.
50% decrease in the product of the maximum perpendicular diameters of the tumor), stable disease (SD) (< 50% decrease or < 25% increase in the product of the maximum perpendicular diameters of the tumor), or progressive disease (PD) (
