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Keywords:

  • soft tissue sarcoma;
  • thigh compartments;
  • morbidity;
  • surgery;
  • radiation

Abstract

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Conflict of Interest Disclosures
  7. REFERENCES

BACKGROUD:

The authors sought to determine whether differences existed in patterns of outcome and morbidity between the 3 thigh compartments after limb-sparing surgery and postoperative radiation therapy (RT).

METHODS:

A total of 255 patients with primary soft tissue sarcoma (STS) of the thigh were identified in our sarcoma database (1982–2002). More than 80% of tumors were >5 cm, high grade, and deep; 33% had close or positive microscopic resection margins. Adjuvant RT consisted of brachytherapy alone (BRT; 63%), external beam RT alone (EBRT; 31%), or a combination of brachytherapy and EBRT (6%). There were 125 anterior, 58 medial, and 72 posterior lesions. The 3 compartments were balanced as to tumor grade, size, depth, margin status, and RT type.

RESULTS:

Overall local control (LC) was 89%, distant metastases-free survival (DMFS) was 61%, and overall survival (OS) was 66% at 5 years (median follow-up, 71 months). Overall rates for complications at 5 years were wound reoperation (10%), edema (13%), joint stiffness (12%), nerve damage (8%), and bone fractures (7%). Wound reoperation and edema were significantly higher for medial-compartment tumors (P = .01 and .005, respectively), whereas nerve damage occurred more frequently in posterior-compartment tumors (P < .001). There were no differences among bone fracture, joint stiffness, DMFS, or OS rates between compartments.

CONCLUSIONS:

Although tumor control was similar for all 3 compartments, more wound reoperation and edema were observed in the medial compartment, and more nerve damage was noted in the posterior compartment. These results may help guide decisions concerning current patients and improve the design of future treatments tailored to compartments. Cancer 2009. © 2008 American Cancer Society.

Surgery and adjuvant radiation have been well established as the standard of care for most high-risk soft-tissue sarcomas of the extremities because of the excellent local control achieved.1-3 Recent studies have focused on factors influencing morbidity. A randomized trial by the National Cancer Institute of Canada (NCIC) showed that wound complications were twice as common with preoperative versus postoperative external-beam radiation therapy, although locoregional control and progression-free survival rates were the same.2 Davis et al. showed a trend toward more fibrosis, edema, and joint stiffness that impacted physical disability in patients treated with postoperative radiation therapy.4 Several studies have found differences in outcome based on tumor location. In a previous report from Memorial Sloan-Kettering Cancer Center (MSKCC), wound complications were more common with a lower versus upper extremity location.5 By using the Musculoskeletal Tumor Society Score (MSTS) and Toronto Extremity Salvage Score (TESS),6 Gerrand et al. found worse functional outcome for deep versus superficial soft-tissue sarcomas in the lower extremity.

Anatomically, the thigh is divided into an anterior, a medial, and a posterior compartment. Each compartment is uniquely characterized by its critical anatomical structures, eg, the femur and femoral nerve in the anterior compartment, the femoral vessels in the medial compartment, and the sciatic nerve in the posterior compartment. Whereas differences in morbidity between the thigh compartments may appear intuitive, the current study sought to determine whether these differences become distinct patterns of outcome and morbidity in a group of patients with primary thigh soft-tissue sarcoma treated with limb-sparing surgery and postoperative radiation therapy at a single institution.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Conflict of Interest Disclosures
  7. REFERENCES

Patients

A review of the prospective adult (aged ≥16 years) database at MSKCC between August 1982 and October 2002 identified 257 patients with primary soft-tissue sarcoma of the thigh that was treated with limb-sparing surgery and postoperative radiation therapy. Patients were excluded when they had had an amputation, distant metastases at presentation, or when surgery or radiation therapy were performed outside MSKCC. Two patients did not have detailed information on the compartment, from which the sarcoma arose, and were excluded from the analysis. A total of 255 patients were, therefore, analyzed. The clinical, pathologic, and treatment characteristics of these patients are summarized in Table 1.

Table 1. Patient Characteristics
CharacteristicNo. (%)
  1. RT indicates radiotherapy; BRT, brachytherapy; EBRT, external beam RT.

Age, y
 ≤50126 (49)
 >50129 (51)
Depth
 Superficial18 (7)
 Deep237 (93)
Grade
 Low45 (18)
 High210 (82)
Size, cm
 ≤10123 (48)
 >10132 (52)
Compartment
 Anterior125 (49)
 Medial58 (23)
 Posterior72 (28)
Positive/close margin
 Yes83 (33)
 No172 (67)
RT type
 BRT160 (63)
 EBRT79 (31)
 BRT + EBRT16 (6)
Conventional RT dose
 Yes218 (85)
 No37 (15)

The median age at diagnosis was 51 years (range, 17 years to 88 years). On the basis of microscopic examination, the surgical margins were considered positive when a tumor extended to the margin and close when a tumor was within <1 mm of the surgical margin. Tumor size was defined as the maximal diameter of the tumor at pathologic analysis. A deep location of a tumor (versus superficial location) was defined as any invasion of or through the superficial fascia.

Treatment

The surgical technique used in this study has been previously described.7 In brief, all visible or palpable tumor was resected in an en bloc fashion. Previous biopsy scars and drain sites, when present, were included in the resection. When the tumor was intermuscular or intramuscular, resection included 1 or more of the involved muscle bundles. The aim was a 1–2 cm margin in all directions, with limitations (<1 cm) aimed at preservation of all major neurovascular structures.

All 255 patients received postoperative radiation therapy at MSKCC. Postoperative brachytherapy alone was given to 160 (63%) patients, postoperative external-beam radiation therapy alone to 79 (31%) patients, and a combination of brachytherapy and external-beam radiation therapy to 16 (6%) patients. The technique of brachytherapy has been previously described.3 In brief, the brachytherapy technique used afterloading catheters, which were placed intraoperatively in the tumor bed and simultaneously evaluated by the surgeon and radiation oncologist. During the study period, brachytherapy was offered to most patients with primary high-grade, soft-tissue sarcoma of the thigh, as long as the geometry of the tumor bed allowed satisfactory placement of the afterloading catheters. In our patient population, the target region to be irradiated was determined by adding 2.0 cm to the superior and inferior dimensions of the resected tumor bed, with 1.5–2.0 cm added in the medial and lateral directions. The afterloading catheters were placed intraoperatively, approximately 1 cm apart, in the tumor bed. The catheters were fixed in position in the target region by absorbable sutures and secured to the skin at the catheter exit site with buttons and nonabsorbable sutures. A drain was placed over the tumor bed, and the wound was closed in layers. Postoperatively, localization films were obtained, and computerized dosimetry was performed.

The median dose of brachytherapy alone was 45 Gy (range, 0.58 Gy to 55 Gy), with a median dose rate of 0.41 Gy per hour. When brachytherapy was used as a boost (n = 16), the median dose was 20 Gy (range, 15 Gy to 45 Gy), and the median external-beam radiation therapy dose was 45.9 Gy (range, 24 Gy to 66 Gy). When external-beam radiation therapy alone was delivered, the median dose was 64.8 Gy (range, 39.6 Gy to 75 Gy) at 1.8–2.0 Gy per fraction. The initial target volume for external-beam radiation therapy included the tumor bed plus a 5–10 cm margin to a dose of 40–45 Gy. This was usually followed by 1 or 2 cone downs to bring the median total dose to 64.8 Gy.

Of the 255 patients who received postoperative radiation therapy, 218 (85%) received a “conventional” radiation dose, defined as 45 Gy for brachytherapy alone, 60 Gy to 70 Gy for external-beam radiation therapy alone, and 15 Gy to 20 Gy in combination with 45 Gy to 50 Gy, respectively, for patients treated with brachytherapy plus external-beam radiation therapy. This strict definition of the conventional dose was implemented to minimize the potential influence of large variation in the radiation-therapy dose on outcome.

Adriamycin-based chemotherapy was given to 78 (31%) patients. Patients who received chemotherapy typically had tumors >10 cm or were generally part of early in-house protocols evaluating the role of adjuvant chemotherapy. Therefore, the influence on chemotherapy on outcome was not evaluated in the current study.

Complications

Complications were assessed in terms of wound reoperation, joint stiffness (mild, moderate, severe), edema (mild, moderate, severe), peripheral nerve damage (excluding patients who required resection of a major nerve as part of their oncologic surgery), and bone fracture. Nerve damage was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 criteria (grade 1, asymptomatic neuropathy; grade 2, symptomatic neuropathy not interfering with activities of daily living [ADLs]; grade 3, neuropathy interfering with ADLs; grade 4, disabling or life-threatening neuropathy).

Statistical Analysis

The time of follow-up was calculated from the date of the first operation at MSKCC. The median follow-up time for all 255 patients was 71 months. In patients who were still alive at their last follow-up visit, the median follow-up time was 108 months. Local recurrence was defined as any recurrence in the primary site, regardless of distant recurrence.

Association between variables was tested by using the chi-square test. For variables with few observations, Fisher exact test was used.8 The survival rates and actuarial complication rates were calculated by the Kaplan-Meier product-limit method.9 Comparisons of survival curves were performed by the log-rank test.10 A multistep Cox regression analysis was used for multivariate analysis of predictive factors for local control (LC) and morbidities.11

RESULTS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Conflict of Interest Disclosures
  7. REFERENCES

Patients

The 3 groups of patients with tumors in the anterior, medial, and posterior compartment of the thigh were balanced by sex, age, depth, grade, size, margin status, radiation therapy type, and radiation dose (Table 2). There was, however, a significant difference in the rate of vessel resection and nerve resection or neurolysis between compartments. The rate of vessel resection was 38% for the medial compartment versus 12.5% for the posterior and 9% for the anterior compartment (P < .0001). The rate of nerve resection or neurolysis was 36% for the posterior compartment versus 14% for the anterior and 28% for the medial compartment (P = .002). The rate of periosteal stripping or bone resection was 21% for the anterior compartment versus 12% for the medial and 4% for the posterior compartment (P = .005).

Table 2. Compartment Characteristics
 AnteriorMedialPosteriorP
 No. (%)No. (%)No. (%) 
  • RT indicates radiotherapy; BRT, brachytherapy; EBRT, external beam RT.

  • *

    This P-value is based on a Fisher exact test. Chi-square test (which would give a P-value as .02) is no longer valid here because some cells are too sparse, ie, they contain too few observations (or expected number of observations).

Sex
 Womevn60 (48)26 (45)33 (46).91
 Men65 (52)32 (55)39 (54)
Age, y
 ≤5064 (51)24 (41)38 (53).37
 >5061 (49)34 (59)34 (47)
Depth
 Superficial11 (9)3 (5)4 (6).57
 Deep114 (91)55 (95)68 (94)
Grade
 Low21 (17)7 (12)17 (24).22
 High104 (83)51 (88)55 (76)
Size, cm
 ≤1067 (54)25 (43)31 (43).24
 >1058 (46)33 (57)41 (57)
Positive/close margins
 Yes34 (27)20 (34)29 (40).16
 No91 (73)38 (66)43 (60)
RT type
 EBRT39 (31)21 (36)19 (26).48*
 BRT/BRT + EBRT86 (69)37 (64)53 (74)
Conventional RT dose
 Yes116 (93)53 (91)62 (86).29
 No9 (7)5 (9)10 (14)
Nerve status
 Intact107 (86)42 (72)46 (64).002
 Neurolysis/Resection18 (14)16 (28)26 (36)
Vessel resection
 No114 (91)36 (62)63 (87.5)<.0001
 Yes11 (9)22 (38)9 (12.5)
Bone status
 Intact99 (79)57 (88)69 (96).005
 Stripping/Resection26 (21)7 (12)3 (4)

Tumor Control

Of the 255 patients, 9% (n = 24) developed local recurrence; 12 of 125 (10%) in the anterior, 8 of 58 (14%) in the medial, and 4 of 72 (6%) in the posterior compartment. The overall 5-year LC rate was 89% (95% CI, 85.1%–93.6%). There was no statistically significant difference in LC across compartments. The rate was 90% (95% CI, 84%–96%) for the anterior, 84% (95% CI, 74%–94%) for the medial, and 91% (95% CI, 83%–99%) for the posterior compartment (P = .3) as shown in Figure 1. Tumor size and margin status did not significantly influence LC. The percentage of patients free of local recurrence at 5 years for ≤10 cm and >10 cm tumors was 90.5% (95% CI, 84.7%–96.3%) and 88.2% (95% CI, 81.9%–94.4%), respectively (P = .39). In patients with a margin-negative resection, the percentage of patients free of local recurrence at 5 years was 91.4% (95% CI, 86.8%–96.0%) versus 85.1% (95% CI, 76.2%–94.0%) for those with a close and positive margin (P = .14). The overall 5-year distant metastases-free survival was 61% (95% CI, 54%–67%), and overall survival was 66% (95% CI, 60%–72%). Anatomic compartment did not significantly impact distant metastases-free survival (P = .3) nor overall survival (P = .5).

thumbnail image

Figure 1. Local control for primary soft tissue sarcoma of the thigh according to compartment is depicted.

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Wound Reoperation

Wound complications requiring reoperation developed in 9% of patients (n = 24), with 6 of 125 (5%) tumors arising from the anterior, 10 of 58 (17%) from the medial, and 8 of 72 (11%) from the posterior compartment. The overall 5-year actuarial rate for wound reoperation was 10% (95% CI, 6%–14%). The rate of wound reoperation was significantly influenced by compartment. The 5-year actuarial rates were 4.9% (95% CI, 1.0%–8.8%) for the anterior compartment and 14.6% (95% CI, 8.2%–20.9%) for the medial and posterior compartments (P = .014) as shown in Figure 2A. The influence of other potential prognostic factors on wound reoperation was also assessed. Higher rates of wound reoperation were associated with the use of brachytherapy versus external-beam radiation therapy (12.4% vs 3.9%, respectively; P = .046), older age (14.1% for >50 years vs 5.7% for ≤50 years; P = .03), and whether vessel resection was performed (20.5% with vessel resection vs 7.9% without vessel resection; P = .01). On multivariate analysis, the medial and posterior compartment were marginally significant (P = .057), but age >50 years, brachytherapy, and vessel resection were all independent predictors of the need for wound reoperation (Table 3).

thumbnail image

Figure 2. Graphs represent (A) actuarial wound reoperation according to compartment, (B) actuarial edema according to compartment, and (C) actuarial nerve damage according to compartment (excluding patients with nerve resection).

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Table 3. Wound Reoperation
 Univariate AnalysisMultivariate Analysis
5-Year Probability (95% CI)PHazard RatioP
  1. CI indicates confidence interval; NS, not significant; RT, radiotherapy; BRT, brachytherapy; EBRT, external beam RT.

Compartment
 Anterior4.9 (1.0 to 8.8).010.397.057
 Medial/posterior14.6 (8.2 to 20.9)
Age
 ≤505.7 (1.5 to 9.9).032.439.048
 >5014.1 (7.8 to 20.4)   
Sex
 Women10.5 (4.8 to 16.2).70 NS
 Men9.2 (4.1 to 14.3)
Size, cm
 ≤107.4 (2.6 to 12.2).22 NS
 >1012.2 (6.3 to 18.1)   
RT type
 EBRT3.9 (0.0 to 8.3).0463.624.038
 BRT12.4 (7.3 to 17.5)
Adjuvant chemotherapy
 Yes7.6 (1.6 to 13.6).47 NS
 No10.8 (6.0 to 15.6)
Vessel resection
 Yes20.5 (10.9 to 37.0).012.410.050
 No7.9 (4.9 to 12.5)

Edema and Joint Stiffness

Edema developed in 34 (13%) patients, with 13 of 125 (10%) tumors located in the anterior, 13 of 58 (22%) in the medial, and 8 of 72 (11%) in the posterior compartment. The overall 5-year actuarial rate of edema was 13% (95% CI, 8%–17%). Twelve patients had mild edema; 17 patients had moderate edema; and 5 patients had severe edema. The percentage of patients with edema at 5 years was significantly higher for medial (25.7%; 95% CI, 12%–39%) than for anterior and posterior compartment tumors (9.0%; 95% CI, 4.7%–13.5%; P = .005) as shown in Figure 2B. Compared with brachytherapy, external-beam radiation therapy was associated with a higher percentage of patients with edema at 5 years (5.7% vs 26.7%, respectively; P < .0001). Other predictors were female sex, tumor size >10 cm, and vessel resection. On multivariate analysis, only medial-compartment tumors, female sex, and external-beam radiation therapy were independent predictors of edema (Table 4).

Table 4. Edema
 Univariate AnalysisMultivariate Analysis
5-Year Probability (95% CI)PHazard ratioP
  1. CI indicates confidence interval; NS, not significant; RT, radiotherapy; BRT, brachytherapy; EBRT, external beam RT.

Compartment
 Medial25.7 (15.1 to 41.5).0052.05.044
 Anterior/posterior9.0 (5.67 to 14.5)   
Age, y
 ≤5013.0 (8.0 to 20.8).48 NS
 >5011.9 (7.0 to 19.7)   
Sex
 Women19.1 (12.7 to 28.1).0082.51.015
 Men6.3 (3.2 to 12.2)   
Size, cm
 ≤106.3 (3.0 to 12.8).002 NS
 >1018.8 (12.6 to 27.7)   
RT type
 BRT5.7 (3.0 to 10.8)<.00015.20<.0001
 EBRT26.7 (17.8 to 38.8)   
Vessel resection
 Yes29.4 (16.6 to 48.6).003 NS
 No9.3 (5.9 to 14.5)   

Joint stiffness developed in 13% of patients (n = 32), with 16 of 125 (13%) tumors arising from the anterior, 5 of 58 (9%) from the medial, and 11 of 72 (15%) from the posterior compartment. The overall percentage of patients with joint stiffness at 5 years was 12% (95% CI, 7.4%–16%). Joint stiffness was mild (19 patients), moderate (9 patients), or severe (3 patients). For 1 patient, the grade of joint stiffness was unknown. Unlike with wound reoperation and edema, the compartment did not impact the rate of joint stiffness (12.9% anterior, 95% CI, 6.7%–19.2%; 9.3% medial, 95% CI, 1.4%–17.3%; 10.7 % posterior compartment, 95% CI, 3%–18.3%; P = .35). Joint stiffness was significantly associated with large tumor size (19.0% for >10 cm vs 4.3% for ≤10 cm; P = .0001) and type of radiation therapy (external-beam radiation therapy 27.0% vs brachytherapy 4.6%; P < .0001). Those 2 factors remained independent predictors of joint stiffness on multivariate analysis (external-beam radiation therapy hazard ratio [HR], 2.9; P = .02; brachytherapy HR, 6.1; P < .0001).

Nerve Damage and Bone Fracture

Nerve damage was assessed only in patients who did not undergo nerve resection at the time of operation (n = 227). Of these 227 patients, 20 (9%) developed nerve damage, with 5 of 115 (4%) tumors arising from the anterior, 2 of 47 (4%) from the medial, and 13 of 65 (20%) from the posterior compartment. The overall actuarial rate of patients with nerve damage at 5 years was 8% (95% CI, 4.4%–12.2%). There were 7 patients with grade 1, 2 patients with grade 2, 2 patients with grade 3, and 9 patients with grade 4 nerve damage. The percentage of patients with nerve damage at 5 years was significantly higher in patients with posterior (21.1%; 95% CI, 10.2%–32.0%) versus anterior and medial compartment tumors (3.5%; 95% CI, 0.4%–6.6) (P < .001) as shown in Figure 2C. The only other predictor of nerve damage was neurolysis. The percentage of patients with nerve damage at 5 years was 27.0% versus 5.2% for patients with versus patients without neurolysis at the time of operation (P = .0003). On multivariate analysis, a posterior-compartment tumor location and neurolysis were independent predictors of nerve damage (Table 5).

Table 5. Nerve Damage Excluding Patients With Nerve Resection
 Univariate AnalysisMultivariate Analysis
5-Year Probability (95% CI)PHazard ratioP
  1. CI indicates confidence interval; NS, not significant; RT, radiotherapy; BRT, brachytherapy; EBRT, external beam RT.

Compartment
 Anterior/medial3.5 (0.4 to 6.6)<.0014.660.002
 Posterior21.1 (10.2 to 32.0)
Age, y
 ≤509.5 (3.7 to 15.3).23 NS
 >506.9 (1.8 to 12.0)   
Sex
 Women8.9 (3.1 to 14.7).51 NS
 Men7.9 (2.4 to 13.4)   
Size, cm
 ≤106.8 (1.8 to 11.8).25 NS
 >109.7 (3.9 to 15.5)
RT type
 EBRT7.2 (0.1 to 14.3).71 NS
 BRT8.6 (4.0 to 13.2)
Adjuvant chemo
 Yes4.5 (0.0 to 9.6).13 NS
 No9.9 (4.8 to 15.0)
Neurolysis
 Yes27.0 (10.6 to 43.4).00032.870.026
 No5.2 (1.8 to 8.6)

Bone fracture developed in 15 (6%) patients, with 10 of 125 (8%) tumors arising from the anterior, 2 of 58 (3%) from the medial, and 3 of 72 (4%) from the posterior compartment. The overall percentage of patients with fracture at 5 years was 6.9% (95% CI, 3.1%–10.7%). Although there were more fractures at 5 years in the anterior (8.6%; 95% CI, 3.0%–14.2%) versus the medial and posterior compartment (5.1%; 95% CI, 0.0%–10.1%), this difference was statistically insignificant (P = .25). Bone fractures occurred more frequently in patients who had surgical manipulation of the femur. The rate was 24.8% (95% CI, 7.8%–41.8%) when the periosteum was stripped or the bone was resected versus 4.1% (95% CI, 0.8%–7.4%) in patients with an intact femur (P< .0001). Other significant predictors of fracture on univariate analysis were external-beam radiation therapy instead of brachytherapy, age >50 years, and female sex. On multivariate analysis, all these factors retained their independence except for external-beam radiation therapy (Table 6).

Table 6. Bone Fractures
 Univariate AnalysisMultivariate Analysis
5-Year Probability (95% CI)PHazard ratioP
  1. CI indicates confidence interval; NS, not significant; RT, radiotherapy; BRT, brachytherapy; EBRT, external beam RT.

Compartment
 Anterior8.6 (3.0 to 14.2).25 NS
 Medial/posterior5.1 (0.0 to 10.1)
Age, y
 ≤502.9 (0.0 to 6.2).033.300.045
 >5012.3 (4.7 to 19.9)
Sex
 Women11.0 (4.4 to 17.6).024.250.026
 Men2.9 (0.0 to 6.3)
Size, cm
 ≤104.1 (0.0 to 8.2).15 NS
 >1010.0 (3.5 to 16.5)
RT type
 EBRT13.4 (4.4 to 22.4).01 NS
 BRT3.7 (0.3 to 7.1)
Adjuvant chemotherapy
 Yes7.7 (0.9 to 14.5).89 NS
 No6.5 (2.0 to 11.0)
Bone status
 Intact4.1 (0.8 to 7.4)<.00017.100.0003
 Manipulated24.8 (7.8 to 41.8)

DISCUSSION

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Conflict of Interest Disclosures
  7. REFERENCES

Reducing morbidity from adjuvant therapy in oncology is an important task. Soft-tissue sarcoma can arise from any part of the body; thus, general toxicity data are of little help to the individual patient. Knowledge has accumulated that allows for better estimation of morbidity in extremity versus nonextremity sites and between extremity locations ie, upper versus lower.5, 6 In the current study, the aim was to study morbidity and outcome in soft-tissue sarcoma of the thigh. Thigh sarcoma, about one-third of all sarcomas, represents an ideal target for such investigation because of its 3 unique anatomical compartments and high incidence.12, 13

In the current study, the 5-year LC rate was 89%, similar to other reports.2, 7, 14 There was no statistically significant influence of the compartment on the 5-year LC rates in this study; 90% for the anterior, 84% for the medial, and 91% for the posterior compartment (P = .3). Distant metastases-free survival and overall survival rates were not influenced by compartment. Compartments were balanced by age, grade, tumor size, depth, and margin status; this is consistent with comparable tumor control according to compartment. Data on complications by thigh compartment are scant. In the current study, the rate of wound reoperation was associated with medial and posterior versus anterior compartment tumors (14.6% vs 4.9%; P = .01). On multivariate analysis, the use of brachytherapy, age >50 years, and vessel resection were independent predictors of wound reoperation. Significant wound complications that require reoperation have previously been shown to be influenced by radiation therapy parameters and tumor location. In the NCIC trial,2 the rate of wound complication was significantly higher with preoperative (35%) versus postoperative (17%) radiation therapy (P = .01). In the brachytherapy trial from MSKCC, the timing of brachytherapy after surgery also had a significant impact on wound complication.15, 16 Pradhan reported a 36% incidence of wound complications, including seroma, purulent discharge, and wound reoperation in soft-tissue sarcoma of the adductor compartment. Although the rate of wound complication was high in his study, no comparison to other thigh compartments was made.17

Because the majority of venous and lymphatic drainage runs through the medial compartment of the thigh, it is not surprising that the rate of edema was significantly higher in that compartment (25.7%) versus the anterior and posterior compartments (9.0%). Cannon et al. identified an anatomical correlation between higher rates of chronic complications, including edema, and a proximal tumor location in the groin or proximal thigh.18 Other risk factors for edema that have been reported in the literature include larger radiation therapy portals and radiation-therapy doses ≥60 Gy to 63 Gy.19 In contrast to wound reoperation and edema, the unique anatomical features of the 3 thigh compartments did not impact joint stiffness in our study (P = .35). Only the use of external-beam radiation therapy and tumor size >10 cm were independent predictors of joint stiffness. The rate of bone fracture was not significantly influenced by compartment either (8.6% for anterior vs 5.1% for medial and posterior compartments), but was independently affected by age >50 years, female sex, and bone manipulation. Other investigators have also shown a correlation to fracture risk of higher radiation therapy doses of 60 Gy to 66 Gy, periosteal stripping, female sex, and radiation therapy to the entire circumference of the bone.18, 20

In the current study, when patients with documented nerve resection were excluded, the overall incidence of nerve damage at 5 years was 8.3%. Other investigators have also reported nerve damage rates between 2% and 7%.21, 22 In the current study, the rate of nerve damage was significantly influenced by compartment (21.1% for posterior vs 3.5% for anterior and medial compartments; P < .001). On multivariate analysis, tumor location in the posterior compartment retained its independent status as a predictor of nerve damage. The length that the sciatic nerve traverses in the posterior compartment of the thigh and the high rate of pre-existing sciatica in the general population (13% to 40%)23 may partly explain the high likelihood of incurring an injury from treatment.

In conclusion, soft-tissue sarcoma of the thigh has distinct patterns of morbidity based on its anatomical compartment of origin. Although tumor control was similar for all 3 compartments, more wound reoperation and edema were observed in the medial compartment, and more nerve damage was noted in the posterior compartment. These data identify patients at high risk for wound complications and, thus, those who may benefit from tissue transfer. The remaining complications, eg, edema and nerve damage, are consistent with the anatomical contents and risks in each compartment. These data provide information that can lead to more adequate counseling and surveillance of patients, that can help guide decisions on the best treatment approach, and that can help early recognition of morbidities, which, in turn, should lead to prompt initiation of rehabilitative care.

REFERENCES

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Conflict of Interest Disclosures
  7. REFERENCES
  • 1
    Pisters PW,O'Sullivan B,Maki RG. Evidence-based recommendations for local therapy for soft tissue sarcomas. J Clin Oncol. 2007; 25: 1003-108.
  • 2
    O'Sullivan B,Davis AM,Turcotte R, et al. Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial. Lancet. 2002; 359: 2235-2241.
  • 3
    Alektiar KM,Leung D,Zelefsky MJ,Healey JH,Brennan MF. Adjuvant brachytherapy for primary high-grade soft tissue sarcoma of the extremity. Ann Surg Oncol. 2002; 9: 48-56.
  • 4
    Davis AM,O'Sullivan B,Turcotte R, et al. Late radiation morbidity following randomization to preoperative versus postoperative radiotherapy in extremity soft tissue sarcoma. Radiother Oncol. 2005; 75: 48-53.
  • 5
    Alektiar KM,Brennan MF,Singer S. Influence of site on the therapeutic ratio of adjuvant radiotherapy in soft-tissue sarcoma of the extremity. Int J Radiat Oncol Biol Phys. 2005; 63: 202-208.
  • 6
    Gerrand CH,Wunder JS,Kandel RA, et al. The influence of anatomic location on functional outcome in lower-extremity soft-tissue sarcoma. Ann Surg Oncol. 2004; 11: 476-482.
  • 7
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