Brachytherapy: Applications and Technique, 1st Edition

10. Soft Tissue Sarcoma Brachytherapy

 

Chandrajit P. Raut

Michele Albert

Introduction

Brachytherapy (BT) is a treatment modality in which radioactive isotopes are placed in close proximity to or directly into tumors. Soft tissue sarcomas (STS) are rare tumors that account for approximately 1% of all adult malignancies. Their anatomic distribution is illustrated in Figure 10.1. Treatment of STS is complicated by their proclivity for local recurrence after attempted curative resection. Local recurrence rates of up to 50% have been reported.1 In an effort to minimize rates of local failure, radical resection or amputation was routinely considered. In fact, between 1949 and 1968, 47% of 297 patients treated for extremity STS at Memorial Sloan-Kettering Cancer Center (MSKCC) underwent amputation.2 Nevertheless, the 5-year survival rate in this series was only 45%, suggesting that such radical surgery is not curative. Therefore, strategies for local control without extensive resection or amputation have been investigated. Changes in surgical management (compartment or muscle group resection) coupled with developments in adjuvant therapy over the last three decades (pre- or postoperative external beam radiation therapy [EBRT], isolated limb perfusion or intraarterial infusion, and BT) have altered the surgical approach to STS.

Sarcomas were previously regarded as highly radioresistant tumors, a view dispelled by modern megavoltage therapy.4 In vitro experiments at the Massachusetts General Hospital and the University of Chicago have shown that the fraction of cells surviving a single dose of radiation of 2 Gy is similar to that for adenocarcinoma of the breast.5

Contemporary Management of Localized Soft Tissue Sarcomas

A multidisciplinary approach combining conservative surgery with EBRT has largely replaced radical surgery on account of studies showing comparable local control rates and better cosmetic and functional results with the former. In a retrospective analysis, Tepper and Suit identified similar local relapse rates of 18.1% in 464 cases of STS treated by radical surgery and 18.3% in 416 cases treated with wide resection and radiotherapy.6 Metastatic rates of 31.5% and 22.6%, respectively, confirmed that survival was not compromised. Rosenberg et al. at the National Cancer Institute (NCI) prospectively randomized patients with high-grade STS of the extremity to amputation or wide resection plus radiation.7 At 5 years, there were no local recurrences in the amputation arm and 4 (15%) local recurrences of 27 patients in the limb-sparing resection arm (p = 0.06). More importantly, there was no difference in overall survival (OS). This phase III study established limb-sparing surgery as the standard approach to patients with localized extremity disease.

 

Figure 10.1 Anatomic distribution of soft tissue sarcomas.3.

Once the more conservative multidisciplinary approach was established, investigators explored the impact of radiation therapy (RT) and its timing on outcome. Yang et al. randomized patients treated with wide resection to receive postoperative EBRT or no further adjuvant therapy.8 This phase III study demonstrated improved local control after resection plus radiation compared with resection alone, but no significant change in OS. In a retrospective study comparing preoperative and postoperative EBRT, Pollack et al. reported that preoperative radiation was associated with improved local control for patients with measurable disease.9

Henschke et al. first described the concept of BT through placement of catheters with radioactive implants, for patients with STS.10 Forty-three patients with predominantly head and neck STS were treated with a variety of implants, including radon radium 222 (222Ra), gold 198 (198Au), and iridium 192 (192Ir) implants.10 The role of tumor bed BT in the management of adult extremity STS with limb- and function-sparing therapy was first described by Ellis and by Collins et al.11,12 and expanded at MSKCC.

Advantages of Brachytherapy over External Beam Radiation Therapy

BT offers several advantages over conventional EBRT (see Table 10.1). First, treatment is delivered over a shorter course, generally over 4 to 6 days, thereby allowing the patient to leave the hospital after a 10- to 14-day stay, having completed both surgery and BT. Such logistics of administering radiation make the therapy easier for patients, especially for those living far from the center where they are treated. Second, as a consequence of its shorter treatment course, BT has socioeconomic advantages. As per a 1994 report, treatment with BT afforded financial savings of $1000.00 (US) per patient compared with EBRT.13Third, because the tumor cells are still relatively well oxygenated and well nourished, and therefore more susceptible, there is enhanced radiobiologic effectiveness with BT than with postoperative EBRT. Fourth, by placing radioactive isotopes in close proximity to or directly into tumors, high doses of radiation may be delivered to the tumor or tumor bed while minimizing the doses to surrounding normal tissues.14 In general, the overlying skin, drain site(s), and the remainder of muscle compartment are not treated. Such high radiation doses to the tumor bed with sparing of surrounding tissue results in fewer normal tissue complications.15 Finally, the manner of delivery enables direct visualization of the tumor bed and the surrounding critical structures.16

Table 10.1 Advantages of Brachytherapy Over External Beam Radiation Therapy in the Treatment of Soft Tissue Sarcomas

Shorter treatment course (4–6 d)
Less expensive
Enhanced radiobiologic effectiveness
High dose to target with relative sparing of surrounding normal tissue
Direct visualization of the tumor bed and the surrounding critical structures

Oncologic Considerations

The care of sarcoma patients can be improved with the use of a multidisciplinary approach to therapy. This is particularly evident in the administration of BT. The precise mapping of the extent of the target tumor bed and the surrounding critical neurovascular and bony structures requires joint decision making by the surgeon and radiation oncologist in the operating room.

Traditional endpoints may be used to evaluate the efficacy of current treatment strategies. These include rates of local and distant failure, disease-free survival (DFS), and OS, as well as complication rates. Perhaps the most critical outcome in evaluating the efficacy of RT in the treatment of STS is local control. Local failure correlates with distant failure. Habrand et al. of Institut Gustave-Roussy reported that distant metastases developed in 60% of patients with STS with local failure and in only 26% of those with local control.17 In turn, distant failure translated into poorer survival.

Several oncologic factors must be evaluated by the multidisciplinary sarcoma team to determine whether RT in general is indicated, and if so, whether BT alone, EBRT alone, or combined BT and EBRT is the most appropriate treatment option. BT improves local control for high-grade tumors, but not low-grade tumors.14,18,19 Surgical resection margin status has a significant impact on disease recurrence. Tanabe et al. reported that, in 95 patients with extremity STS treated with preoperative EBRT, the 5-year local control rate was 62% with positive margins and 91% with negative margins (p = 0.005).20 Additional studies suggest that tumors in certain locations demonstrate a greater propensity to recur locally.21 The anatomic distribution of common STS is shown in Figure 10.1. On the basis of currently available data, STS tumor histology is less critical. However, certain tumor histologies are considered high grade.22 Different histologies have different anatomic distributions.

Evidence-Based Management

Determination of the most optimal course of therapy requires the input of both the surgeon and the radiation oncologist. Not all patients with STS require radiation. Patients with tumors appropriate for radiation may be treated with BT or EBRT, as demonstrated in numerous studies. However, no prospective trials have directly compared BT and EBRT for either primary or recurrent STS (except for economic endpoints). Furthermore, interpretation of available data is difficult as many of the retrospective studies combine both primary and locally recurrent tumors, and some include patients with R2 resections. Most studies enroll patients with extremity STS. Superficial trunk and head and neck sarcomas are included in several studies. Data on special situations, such as retroperitoneal sarcomas or desmoid tumors, are listed separately.

Retrospective Data

The efficacy of adjuvant BT in the treatment of STS was established in a series of retrospective studies (see Tables 10.2 and 10.3). Several studies included patients primarily treated with surgery and adjuvant BT alone, although others included those treated with surgery and adjuvant BT in conjunction with EBRT for primary and recurrent STS.

Surgery with Adjuvant Brachytherapy Alone

Several studies have evaluated the impact of conservative surgery and adjuvant BT without additional EBRT (Table 10.2). In one of the earliest studies, Collins et al. from the Churchill Hospital in England treated 32 patients with BT. Ten patients required additional EBRT when postoperative images for dosimetry suggested that the implant geometry was unsatisfactory.11 Eleven (34%) of 32 patients had recurrences locally, out of which seven underwent salvage therapy. Nine (26%) patients developed distant metastases, including six who had local recurrences as well. Complication rates were not reported; however, three patients who had BT doses >60 Gy developed radionecrosis.

Table 10.2 Nonrandomized Studies Evaluating Brachytherapy as Adjuvant Therapy for Primary and Recurrent Soft Tissue Sarcomas after Limb-Sparing Surgery

Author

Year

Institution

Patients

Site

Size

High Grade (%)

R0, R1, R2

Primary

Locally Recurrent

Dose (Gy)

Additional EBRT

Median Follow-up (mo)

Complication Rates (%)

Local Control (%)

Function Preserved (%)

Distant Failure (%)

OS

Collins11

1976

Churchill Hospital

32

66

Hilaris23

1985

MSKCC

17

Ext

71% >5 cm

71

R1, R2

17

0

40

34

100

Shiu24

1984

MSKCC

33

Ext

64% >5 cm

70

R1, R2

17

16

Median 40

20–24 Gy (N = 5)

36

39

82a

94

Zelefsky25

1990

MSKCC

45

Ext

64% >10 cm

68

R0, R1, R2

14

Median 44

50 Gy (N = 13)

60

70

84

30%, 5 y

66%, 5 y

Habrand17

1991

Institut Gustave-Roussy

48

Ext, trunk, H + N

25% >5 cm

86

22

22

60

Max 60 Gy (N = 4)

82

35

67

39

58.5%, 5 yb

Chaudhary26

1998

Tata Memorial Hospital

33

30

75

Alektiar21

2002

MSKCC

202

Ext

70% >5 cm

100

R0, R1

202

Median 45

61

20

14

70%, 5 y

R0; margins grossly and microscopically negative; R1, margins grossly negative but microscopically positive; R2, margins grossly positive.
aLocal control was achieved in all 17 patients with primary tumors and 10 (62.5%) of 16 patients with recurrent sarcomas (p = 0.009).
bThe 5-year OS rate was 62% in patients with primary tumors and 56.5% in those previously treated.
EBRT, external beam radiation therapy; OS, overall survival; Ext, extremity; H + N, head and neck; N/A, not applicable. MSKCC, Memorial Sloan-Kettering Cancer Center.

Table 10.3 Nonrandomized Studies Evaluating Brachytherapy and External Beam Radiation Therapy as Adjuvant Therapy for Primary and Recurrent Soft Tissue Sarcomas after Limb-Sparing Surgery

Author

Year

Institution

Patients

Site

Size

High Grade (%)

R0, R1, R2

Primary

Locally Recurrent

Dose (Gy)

Additional EBRT

Median Follow-up (mo)

Complication Rates (%)

Local Control (%)

Function Preserved (%)

Distant Failure (%)

OS

Mills and Hering27

1981

17

Cobalt (N = 14)

Mean 28

17

100

6

Schray28

1990

Mayo Clinic

63

Ext, Trunk, H + N

54% >5 cm

72

 

56

9

15–20

45–50 Gy (N = 61)

Mean 20

25% preop EBRT, 5% postop EBRT

96

Gemer29

1991

University of Kansas

25

36

36

80

Cionini30

1992

University of Florence

48

Ext, Trunk

54% >5 cm

15

R0, R1

33

15

30–50 (with EBRT); 48–64 (no EBRT)

5 Gy preop (N = 3); 15–20 Gy postop (N = 33);

51

6

81a

94

23

O'Connor31

1993

Mayo Clinic

68

40

22

91

Burmeister32

1997

Queensland Radium Institute

12

13–20

Maximum 60–65 Gy (N = 12)

29

42

83

25

83%, 3 y

Chaudhary26

1998

Tata Memorial Hospital

118

40

71

Delannes33

2000

Centre Claudius Regaud & Institut Bergonie

58

Ext, Trunk

R0, R1

58

0

Median 20

45–50 Gy

54

61

89

65%, 5 y

Rosenblatt34

2003

Rambam Medical Center

32

Ext, Trunk, H + N, Abd

88

23 Gy LDR (16) 16 Gy HDR (5)

Median 39.2 Gy (N = 21)

36

16% severe, 19% late

87.5% at implant site

69%, 5 y

Jones35

2002

University of Toronto

55c

RP

64

37

18

42–50 Gy (N = 41)

19

14

80

2

88%, 2 y

R0; margins grossly and microscopically negative; R1, margins grossly negative but microscopically positive; R2, margins grossly positive.
aLocal control rates: 91% with BT + EBRT, 75% with BT alone.
bBT courses were as follows: 23 Gy LDR (N = 16), 16 Gy HDR (N = 5), 45.5 Gy (N = 9 with no EBRT).
cForty-six patients underwent resection; 41 received preoperative EBRT.
EBRT, external beam radiation therapy; OS, overall survival; Ext, extremity; H + N, head and neck; preop, preoperative; postop, postoperative, LDR, low dose rate; HDR, high dose rate.

Hilaris et al. presented the initial MSKCC experience with 17 previously untreated patients with extremity STS managed with limb-sparing surgery and postoperative BT with low dose rate (LDR) 192Ir implantation to the tumor bed.23 It is of note that 13 of 17 had high-grade tumors, and 6 would have required amputation for complete resection of disease. Despite the fact that 15 of 17 patients had positive resection margins, no local recurrences were seen at a median follow-up of 34 months. This study affirmed the efficacy of adjuvant BT in the local control of poor prognosis STS. In another study from MSKCC, Shiu et al. reported on 33 patients with locally advanced extremity STS treated with function-sparing resection and postoperative BT with 192Ir to the tumor bed.24This series included the same 17 patients reported in the prior study as well as an additional 16 patients with local recurrence after prior treatment who were suitable for salvage. After a median follow-up of 36 months, local control was achieved in all 17 patients with primary presentations and in 10 (62.5%) of 16 previously treated patients. Furthermore, two of the six patients who had recurrences had further resection and BT, resulting in an overall local control rate of 88% (29 of 33). Six of 33 patients died of metastatic disease after 8 to 44 months. Strength and range of motion were satisfactory in 19 patients; four had stiffness or weakness and three had wrist or foot drop that required corrective surgery. Wound complications were identified in 13 (39%) of 33 patients. In particular, three patients had extensive soft tissue necrosis, two of which underwent amputation; both of these patients received substantial radiation with both BT and high-dose EBRT. Other wound complications were attributed to thin, poorly vascularized flaps or closures under tension. Several important lessons were learned from this study. First, such therapy was efficacious, even in the setting of recurrent disease. Second, local failures were probably due to either an inadequate radiation dose or an inadequate field size or both.36 Third, functional results were satisfactory. Finally, major wound complications were secondary to excessive doses of radiation or suboptimal wound flaps closure.

Most recently, Alektiar et al. updated the MSKCC experience, reporting the results in 202 patients with high-grade extremity sarcoma treated with limb-sparing surgery and adjuvant BT over 15 years (1982 to 1997).21 With a median follow-up of 61 months, local control and OS rates were 84% and 70%, respectively. The 5-year local control rates for shoulder location, nonshoulder upper extremity, and lower extremity were 44%, 76%, and 91%, respectively. On multivariate analysis, shoulder location, microscopically positive margins of resection, and nonshoulder upper extremity site were found to be independent predictors of poor local control. Complications developed in 41 (20%) of 202 patients. Overall bone fracture rates were 3%; the fracture rates were 28% if bone was resected at the time of surgery, 9% after periosteal stripping, and 1% with intact bone.

Zelefsky et al. evaluated the MSKCC experience with BT specifically for locally invasive tumors abutting or invading major neurovascular structures treated between 1975 and 1987.25 Among the 47 tumors treated, 13 (28%) had pathologic evidence of neurovascular invasion. Thirteen (28%) patients underwent supplemental EBRT because of multiple close/positive margins, suboptimal implant dose or dosimetry, or gross residual disease; 17 patients received systemic doxorubicin-based chemotherapy. The local control rate was 70% (33 of 47). Nine of the 14 local recurrences were within the treatment field of the implanted volume; five of these nine patients had multiple positive margins but did not receive adjuvant EBRT or had inadequate implant dose/dosimetry. Functional outcome was satisfactory in 38 (84%) patients, but 7 required amputations. Four patients suffered sensory loss alone (one patient) or complete motor and sensory loss (three patients) in the treated peripheral nerve. All four had total radiation doses ranging from 91 to 148 Gy (including prior or postoperative EBRT in addition to BT), whereas total doses <90 Gy were not associated with neurotoxicity. This study demonstrated that local control with satisfactory function was possible with limb-sparing surgery and BT even in the presence of neurovascular involvement; devastating complications such as neurotoxicity could be minimized by keeping the total radiation dose below 90 Gy.

Habrand et al. reported the 20-year experience with BT for STS from the Institut Gustave-Roussy.17 Forty-eight patients with primary or recurrent extremity, trunk, or head and neck sarcomas were treated with surgery and BT (four also received EBRT). With a median follow-up of 82 months, the key results were as follows: (a) a locoregional recurrence rate of 33% (2 of 16 were in-field failures; the rest were within same muscle group), (b) radiation necrosis in 17 (35%) of 48 patients (median implant dose of 60 Gy), (c) truncal tumor location as the only independent predictor of local failure on multivariate analysis, and (d) local relapse as the only covariate predictive of metastasis (p <0.01). On the basis of these data, either the BT clinical target volume (CTV) should be extended or EBRT should be added.

Surgery with Adjuvant Brachytherapy and External Beam Radiation Therapy

The infiltrative nature of sarcomas limits the utility of BT alone when the CTV is large. Although BT limits in-field recurrences, local–regional failures outside the field of irradiation are significant. Resection combined with adjuvant EBRT and boost BT is a more commonly used approach, with satisfactory local control (Table 10.3).

The efficacy of limb-sparing surgery and BT combined with supplemental EBRT was demonstrated by Mills and Hering.27 Seventeen patients with STS were treated with conservative surgery and BT, and 14 also received cobalt teletherapy. All tumors had poor prognostic characteristics (size >5 cm, proximity to vital structures, or recurrent disease). With a median follow-up of 28 months, there was only one recurrence, with none in-field. The complication rate was 17%. Limb function was preserved in all extremity STS.

In the Mayo Clinic experience, 63 patients with primary and recurrent STS underwent 65 procedures combining surgery, BT, and in 61 of 65 cases, EBRT.28EBRT was administered preoperatively for larger lesions near bone or neurovascular structures. Local recurrence was identified in 2 (4%) of 56 primary tumors and 3 (33%) of 9 recurrent tumors; only 1 failed within the implanted volume. All local and distant failures occurred in the setting of high-grade tumors. The complication rate was 5% (2 of 40) if BT preceded EBRT and 25% (4 of 16) if EBRT was given preoperatively. The authors concluded that BT combined with EBRT did not increase local morbidity and may enhance local tumor control when compared with either BT or EBRT alone.

Burmeister et al. from the Queensland Radium Institute treated 12 patients with combined BT and EBRT. With a median follow-up of 29 months, there were 2 (17%) local-regional failures, none of which were within the BT field. The complications, identified in 42% of patients, included two fractures and one chronic, nonhealing wound requiring amputation.

Similar data was reported by Gemer et al. from the University of Kansas.29 With a median follow-up of 36 months, 20 (80%) of 25 patients with extremity or superficial trunk STS treated between 1982 and 1987 had no local recurrence. In their multivariate analysis, local failure correlated with the volume of excised tissue exceeding the volume of tissue receiving 65 Gy from combined BT and EBRT. However, when histologic margins were positive, the local recurrence rate was 71%; in fact, all five local recurrences were in patients with positive margins. Therefore, margin-negative resection and careful preoperative planning of the implant volume should improve local control. Acute complications were noted in three patients (infection, edema, drain-site hernia). Chronic complications were noted in six patients (edema, chronically draining wounds, weight-bearing difficulty).

Cionini et al. treated 48 patients (1980 to 1990) with conservative surgery and BT only (12 cases), BT and preoperative EBRT (3 cases, all initially unresectable STS), and BT and postoperative EBRT (33 cases). The local control rate was 81%; local failures correlated with tumor size >5 cm, positive margins, and total radiation dose <69 Gy. There were no acute wound complications, but sclerosis with functional deficit developed in three patients with initially unresectable tumors who received preoperative EBRT with large fractions. Distant metastases were noted in 23% of the patients.

Delannes et al. from the Institut Claudius Regaud, Toulouse, France, and the Institut Bergonie, Bordeaux, France, reported similar success in 58 patients with primary extremity or superficial trunk STS treated with conservative surgery, BT, and EBRT with a 5-year actuarial local control rate of 89% and OS rate of 65%. However, the authors reported significant complication rates. Acute side effects, generally involving wound healing, occurred in 20 (34%) of 58 patients. Late side effects were identified in 16 (27%) of 58 patients. Late side effects included lymphedema (seven patients), grade 2–4 neuropathies (seven patients), limited mobility at a joint (one patient), and vascular stenosis (one patient). Lower limb tumor location correlated with a greater risk of early complications (p = 0.003), although proximity of the tumor to neurovascular structures increased the risk of late complications (p = 0.009).

Chaudhary et al. from Tata Memorial Hospital, Mumbai, India, reported the results of a retrospective study comparing conservative surgery and BT alone to surgery, BT, and EBRT in 151 patients with STS.26 With a minimum follow-up of 24 months, local control was observed in 75% of patients (25 of 33) treated with limited surgery and BT alone and 71% of those treated with surgery, BT, and EBRT. After subsequent salvage therapy, local control rates were 82% and 86%, respectively. Treatment-related complication rates were remarkably <1%.

Rosenblatt et al. reported similar results from the Rambam Medical Center, Haifa, Israel. They treated 32 patients with extremity, superficial trunk, head and neck, and intraabdominal STS with conservative surgery, BT, and in 21 (66%) patients, EBRT. In 27 patients, BT catheters were placed immediately after resection; in 5 patients, catheters were placed postoperatively. The overall local control rate was 87.5%; local control rates were 92% in the 27 patients with catheters placed intraoperatively and 50% in the 5 patients with catheters placed postoperatively. Severe complications such as soft tissue necrosis, fibrosis, and fistula were observed in 5 patients (16%); chronic radiation changes were observed in 6 patients (19%). Lung metastases were identified in 19% of the patients. The 5-year actuarial DFS and OS were 56% and 69%, respectively.

Prospective Data

The retrospective data have demonstrated excellent outcomes with adjuvant BT with or without EBRT in improving local control for STS. However, these studies did not clearly identify which subset of patients with STS requires adjuvant BT for local control. Only a single prospective trial has been conducted. The preliminary and long-term results from this trial from MSKCC have been published in a series of reports (see Table 10.4).14,18,19

Initially, 117 patients with extremity and superficial trunk STS were randomized after R0 or R1 resection to receive either adjuvant BT or no BT, stratified by grade (low vs. high), tumor size (<5 cm vs. >5 cm), tumor location (superficial vs. deep to fascia), extremity site (proximal vs. distal), and presentation (primary vs. recurrent). Exclusion criteria included tumor violation during resection, R2 resection, or major bone or neurovascular resection. Some patients with high-grade tumors were treated with postoperative doxorubicin-based chemotherapy. After a median follow-up of 16 months,18 local recurrences were identified in 2 (4%) of 52 patients in the BT arm and in 9 (14%) of 65 patients who did not receive BT; this difference was not significant (p = 0.06). However, subset analysis of patients with high-grade tumors identified a significant difference in local control: There were no local failures in 41 patients treated with BT, whereas there were 5 (11%) in 47 patients without BT (p = 0.03). There was no survival benefit.

At 5 years, local control was 82% in the BT group and 67% in the no BT group (p = 0.049).14 Local control rates were 90% and 65%, respectively (p = 0.013), in patients with high-grade tumors, but were similar in those with low-grade tumors. The proportion of patients free of distant metastases was 76% in both arms.

In the most recent update with a median follow-up of 76 months, local control was significantly improved in patients receiving adjuvant BT. The 5-year actuarial local control rates in the164 patients enrolled between 1982 and 1992 were 82% in the 78 patients who were treated with BT and 69% in the 86 patients who were not (p = 0.04).19 Even with longer follow-up, the improved local control was again limited to the 119 patients with high-grade lesions (89% vs. 66%, p = 0.0025). Regression analysis in this subset confirmed that age (≤60) and no BT were significant predictors of local recurrence. Tumor size, margin of resection, location, depth, and status at presentation had no significant effect on local recurrence. Five-year distant metastasis-free survival rates were in 83% in the BT group and 76% in the no BT group (p = 0.60). There was no improvement in DFS and OS rates. The chemotherapy regimen administered during the initial part of the trial (1982 to 1987) for high-grade tumors was abandoned after it showed no impact on outcome.38

Table 10.4 Prospective Clinical Trial Randomizing Patients to Brachytherapy or no Brachytherapy After Limb-Sparing Resectiona

Author

Year

Institution

Total Number of Patients

BT Patients

Site

Size

High Grade (%)

R0, R1, R2

Primary

Locally Recurrent

Dose (Gy)

Median follow-up (mo)

Local Control (%)

Brennan18

1987

MSKCC

117

52

Ext, trunk

75 total, 79 BT

R0, R1

45

16

96 BT, 86 no BTb

Harrison14

1993

MSKCC

126

55

Ext, trunk

65% >5 cm (BT), 70% >5 cm (no BT)

80 BT, 74 no BT

R0, R1

91% BT, 84% no BT

9% BT, 16% no BT

42–45

60

82 BT, 67 no BTc

Pisters19

1996

MSKCC

164

78

Ext, trunk

76

82 BT, 69 no BTd

Pisters37

1994

MSKCC

45

22

Ext, trunk

45 BT, 30 no BT >5 cm

0

R0, R1

19 BT, 17 no BT

3 BT, 6 no BT

42–45

67

 

R0; margins grossly and microscopically negative; R1, margins grossly negative but microscopically positive; R2, margins grossly positive.

aInitial results were reported by Brennan et al.18 and have been updated twice.14,19 Pisters et al. also reported a subset of these patients with low-grade lesions only.
bp = 0.06. Benefit limited to high-grade tumors (local control 100% with BT, 89% without BT, p = 0.003).
cp = 0.049. Benefit limited to high-grade tumors (local control 90% with BT, 65% without BT, p = 0.013).
dp = 0.04. Benefit limited to high-grade tumors (local control 89% with BT, 66% without BT, p = 0.0025).

The lack of benefit of BT in patients with low-grade tumors was substantiated in a separate report from this trial.37 Local recurrence was identified in 6 (27%) of 22 patients with low-grade STS who received BT and 5 (22%) of 23 patients who did not (p = 0.60).

Functional outcomes were well preserved in another analysis from this trial.39 Specific parameters measured included isometric muscle torque, gait velocity, cadence, stride length, and single limb stance time symmetry.

The reports from this trial demonstrate that adjuvant BT after R0/R1 resection of extremity and superficial trunk STS, even in the absence of EBRT, improves local control, but has no impact on rates of distant metastatic recurrence or OS. The difference in local control was seen only in patients with high-grade tumors; the adjuvant BT did not benefit those with low-grade tumors. Resection margin status did not impact rates of local control.

Low Dose Rate versus High Dose Rate Brachytherapy

The aforementioned BT studies employed LDR treatment. The LDR radiation is generally administered continuously at 40 to 100 cGy per hour. However, a major limitation with LDR BT is the 4- to 6-day period of continuous isolation in the postoperative period required for dose delivery. Such solitary confinement, interrupted only by limited visitation by family members or nurses, may be troubling for many patients, particularly the elderly, and impractical for the young. Fractionated HDR implants overcome some of the logistic problems with LDR. HDR radiation is delivered twice daily for 5 to 7 days at >1200 cGy per hour. This obviates the need for prolonged shielding and confinement. Further specifics concerning LDR and HDR BT for STS are discussed in detail in the following text.

The results of studies incorporating HDR BT are somewhat difficult to interpret because they group together patients treated for primary and recurrent STS, the total patient numbers remain small, follow-up is short, and a variety of different fractionation regimens are employed. Little data is available regarding the outcomes with HDR BT implants. Alektiar et al. treated 12 patients, predominantly with low-grade STS.40 With a median follow-up of 16 months, the local control rate was 75%. There was a single patient with delayed wound healing. Functional outcomes were satisfactory in all patients. Koizumi et al. treated 16 lesions in 14 patients with resection and HDR alone.41 Local control rates were 75% at 1 year and 48% at 2 years. Of the local failures, 63% were in patients with gross residual disease (R2 resection). Chun et al. treated 17 patients with HDR and EBRT. At a median follow-up of 31 months, the local control was 100%.42 There was one wound dehiscence. Similar local control rates were reported by others after median follow-ups of 12 to 24 months.43,44,45,46Complication rates were similarly low in all studies except the study from Wayne State University study, which described even mild skin and wound complications in its 48% complication rate.43 Additional data are summarized in the American Brachytherapy Society recommendations for BT of STS.47

Sequelae of Treatment

The dose of radiation necessary to sterilize the tumor bed is generally thought to be in the 58- to 66-Gy range.48,49,50 However, the high doses necessary to sterilize the tumor bed may interfere with wound healing or restrict mobility through fibrosis. The reported complication rates are summarized in Table 10.5; specific complications are listed in Table 10.6.

 

Table 10.5 Postoperative Morbidity after Treatment for Soft Tissue Sarcomas

Author

Year

Institution

Surgery

Brachytherapy

EBRT

Number of Patients

Total Morbidity (%)

Severe Morbidity (%)

Skibber

1987

NCI

+

93

34

10

Arbeit51

1987

MSKCC

+

64

33

3

Suit50

1985

MGH

+

Preop

60

28

13

Bryant

1985

Mayo

+

Preop

34

41

17

Leibel

1982

MSKCC

+

Postop

29

17

7

Bryant

1985

Mayo

+

Postop

20

10

0

Shui24

1984

MSKCC

+

+

33

33

27

Arbeit51

1987

MSKCC

+

+

41

44

22

Schray28

1990

Mayo

+

+

Preop

16

25

12

Mills and Hering27

1981

RMH

+

+

Postop

17

17

6

Schray28

1990

Mayo

+

+

Postop

40

5

2

‘+’ indicates the treatment was done; ‘–’ indicates the treatment was not done.
Preop, preoperative; Postop, postoperative; RMH, Royal Marsden hospital.

Acute Wound Complications

Wound complications as per the MSKCC prospective trial from 1982 to 1985 were examined in further detail.51 Among 105 wounds (in 101 patients), the overall complication rates were 44% in those treated with BT and 14% in those without BT (p = 0.0006). Major complications, defined as wound problems requiring operative revision for soft tissue or skin coverage or threatened limb loss, were identified in 22% and 3% of patients in the two groups, respectively (p = 0.002). Moderate complications, defined as wound separation >2 cm, purulent discharge from the wound, hematoma >25 mL, or seroma requiring repeated aspiration or drainage, were identified in 22% and 11%, respectively. Minor complications, defined as wound separation <2 cm, hematoma <25 mL, or seroma <75 mL requiring no more than 3 aspirations, were seen in 7% and 19%, respectively (p = not significant [NS]). No amputations were required.

Table 10.6 Acute Wound Complications and Late Effects Attributable to Brachytherapy

Acute

Wound breakdown
Soft tissue necrosis
Threatened limb
Seroma requiring drainage
Hematoma requiring drainage
Wound infection
Chronic nonhealing wound

Late

Neuropathy/neuralgia/neuritis
Lymphedema
Soft tissue sclerosis/fibrosis
Long bone fracture
Bowel strictures
Osteonecrosis
Vascular stenosis

These observations, showing increased wound complications with the addition of BT, prompted several technical and procedural changes, such as covering the wound with well-vascularized flaps (local, rotational, or myocutaneous) and delaying catheter loading until after the fifth postoperative day (see Table 10.7).

The rationale for delayed catheter loading is supported by several studies. The maximal inhibitory effect of radiation on wound healing occurs during the first 2 postoperative days.52,53 Furthermore, animal experiments have shown that a delay in administration of BT for 1 week after wound closure is accompanied by significant improvement in wound-breaking strength, new H3 hydroxyproline accumulation, and improved force–tension curves.54 Loading catheters no earlier than the fifth postoperative day allows the proliferative phase of wound healing to continue without impairment by radiation-induced reduction in fibroblast populations.34

A second analysis from 1985 to 1987 after institution of the technical changes demonstrated a significant improvement in wound complication rates.54 The rate of major and minor complications was 14% in the BT group, a significant reduction from the prior study (p = 0.05), and similar to the 10% rate in the group not treated with BT (p = NS).

Other analyses have identified additional risk factors contributing to higher complication rates. Combined BT and EBRT resulted in higher rates of wound if the EBRT is delivered preoperatively rather than postoperatively.31,55 Patients with larger resections (ellipse of resected skin >4 cm in width or area of resected skin >100 cm2) had higher complication rates than those with smaller resection specimens.56

The impact of BT on flap reconstruction after STS resection was investigated by Lee et al.57 Between 1991 and 2000, 17 patients underwent resection of extremity or trunk STS, adjuvant BT, and soft tissue reconstruction with free or pedicled flaps. With a mean BT dose of 38 Gy delivered by catheters loaded 5 to 7 days postoperatively, all flaps survived, although one patient required revision of venous thrombosis for flap salvage. The authors recommended placing microvascular anastomoses (for free flap reconstructions) well away from the radiation target area and delaying removal of closed suction drains until after BT catheters were removed, to minimize complications resulting from catheter dislodgement (Table 10.7).

Late Complications

Late complications from BT have been described with either high doses of total radiation (BT and EBRT) or with proximity of STS to neurovascular structures.25,33

Long bone fractures have been reported after limb-sparing surgery and either BT or EBRT or both for STS. In 58 patients with primary STS treated with preoperative EBRT (50.4 Gy) and surgery, there were 4 (8%) pathologic fractures in 52 long bones at risk.58 Stinson et al. found a 6% fracture rate in 145 patients treated with postoperative radiation.59 In a study of 205 patients treated with resection and radiation for thigh STS, periosteal stripping was the only independent risk factor for femoral fracture. The risk of fracture with periosteal stripping was 29% at 5 years.60

Table 10.7 Strategies to Minimize Wound Complications

Load catheters after the fifth postoperative day.
Cover tenuous wounds with well-vascularized flaps (skin grafts, rotational flaps, myocutaneous flaps).
Place microvascular anastomoses away from radiation target area.
Leave closed suction drains in place until they are removed to increase the distance of wound from implant.

Similar long bone fracture rates have been reported with BT, as described in the aforementioned studies. Alektiar et al. reported overall fracture rates of 3%; the fracture rates were 28% if the bone was resected at the time of surgery, 9% after periosteal stripping, and 1% with intact bone.21 In several studies, occurrence of radionecrosis after BT have been reported. Radiation neuritis is another late complication reported with BT. Total radiation dose >90 Gy was associated with sensory and motor neuropathies.25 Late complications from BT are listed in Table 10.6 and are discussed in the preceding text.

Amputations

With the current treatment paradigms emphasizing limb preservation, amputations are relatively uncommon. Amputations have been reported for recurrent disease when limb-sparing salvage therapy after BT was not possible, particularly in the setting of in-field failures.21,25,28 Wound complications, such as persistent nonhealing wounds or extensive soft tissue necrosis, even in the absence of local failure, may necessitate limb amputation.24,32

Patient Selection

The dogma that adjuvant RT is necessary for function-sparing surgery for extremity STS has been reexamined.61,62 Rydholm et al. reported that extremity STS classified as either subcutaneous or intramuscular tumors (as opposed to extramuscular tumors) may be treated by local surgery without adjuvant therapy with a local recurrence rate of <10%.62 Baldini et al. suggested that candidates who may undergo surgery without radiation include those with (a) primary presentation of disease, (b) histologic resection margins of >2 cm in all directions, (c) sites where local recurrence would not preclude function-sparing salvage surgery and RT, and (d) compliance with close follow-up.61 Small, superficial lesions away from neurovascular or skeletal structures may be amenable to single modality therapy, that is, with surgery alone. The suitability of high-grade or deep tumors for surgery alone remains unresolved. These studies suggest that a subset of patients do not require radiation. Specifically, selected patients with small (<5 cm) high- or low-grade STS amenable to R0 resection may not require any adjuvant RT.61,62 However, precise criteria for selecting such patients have not been defined and require further study.

BT may be used as adjuvant monotherapy or boost therapy with EBRT in appropriately selected patients with primary STS. It may be used as adjuvant monotherapy in patients with completely resected, margin-negative (R0) intermediate or high-grade extremity or superficial trunk STS with negative margins.47 Supporting prospective and retrospective data, which group together patients with primary and recurrent tumors, are detailed in the subsequent text. Data from Memorial Sloan Kettering suggest that there is no improvement in local control rates with BT in patients with low-grade tumors, although EBRT alone or in conjunction with BT may be used.18,19

BT in conjunction with supplementary EBRT is more appropriate than BT as monotherapy if the entire tumor bed cannot be treated, if safe delivery of therapeutically meaningful doses with the implant alone exceeds normal tissue tolerance, if margin status is uncertain or positive (R1, microscopically positive, or R2, macroscopically positive), if surgical field contamination may have occurred, or if skin ulceration is present, which may indicate extensive cutaneous spread through lymphatics. BT may also be combined with EBRT in patients with primary STS with intermediate or high-grade tumors irrespective of margin status or deep lesions that are difficult to reach.

BT may be administered in patients with low-grade sarcomas recurrent after EBRT. Skin ulceration or severe fibrosis due to previous therapy are not contraindications to BT, particularly when wound closure may be salvaged with flaps.

 

Pediatric STS presents a unique treatment problem. Iodine 125 (125I) is an attractive alternative to the more commonly used iridium 192 (192Ir), on account of the reduced radiation exposure to caregivers and to critical anatomic structures, such as gonads, thyroid, and bony growth plates (see Chapter 11).

American Brachytherapy Society Recommendations for Brachytherapy of Soft Tissue Sarcomas

The American Brachytherapy Society has developed guidelines for the use of BT in patients with STS.47 General recommendations are summarized in Table 10.8. Several points deserve further emphasis. The volume of tissue that is considered to be at risk for microscopic extension of tumor is defined as the CTV. The CTV should be encompassed by the treatment catheters or seeds. Although it is generally accepted that the CTV includes the tumor bed plus a margin of normal tissue, there is no consensus on the exact size of this margin. In part, the extent of margin depends on whether BT is used alone or in conjunction with EBRT, the specific resection bed anatomy, tolerance of adjacent tissue to radiation, presence of critical normal structures, and various pathologic factors. The dose to critical normal structures (nerve, blood vessel, or bone) may be reduced by separating the radioactive source from these structures using a variety of layering agents, including Gelfoam (Pharmacia & Upjohn Company, Kalamazoo, MI), omentum, or other flaps. However, there is no absolute contraindication to the implant having direct contact with neurovascular structures or bone. Wound complications may be reduced by loading the catheters no sooner than 5 days after wound closure; they may be loaded 2 to 3 days postoperatively if doses of <20 Gy are given. Additional recommendations for patient selection for BT alone and in conjunction with EBRT, adjuvant dose selection, and special situations such as recurrent or pediatric STS are outlined in Table 10.8.

General Principles of Brachytherapy for Sarcoma

The two isotopes most commonly used for BT in patients with STS are 192Ir and 125I. 192Ir can be used as either HDR or LDR, it offers satisfactory efficiency, but its high radiation energy is cumbersome, necessitating significant radiation safety precautions. Furthermore, significant doses of radiation may be delivered to vital organs (gonads, breast, thyroid). A phase I trial of manually afterloaded high intensity 125I temporary implants demonstrated that they were a useful alternative to 192Ir for tumor bed therapy.63 The two isotopes were equivalent in terms of dosimetry calculations and method of preparation of target tissue. The principal advantage of 125I is its low energy (28 kV), making it easier to shield; this makes 125I an excellent option for children with sarcoma. Among its disadvantages are higher cost, shorter half-life and the larger diameter of the seeds and catheters compared with the LDR 192Ir (see Table 2.1).

Table 10.8 General Recommendations from the American Brachytherapy Society

Assess patients in a preoperative multidisciplinary setting to determine the treatment
Determine CTV by radiographic, surgical, and pathologic findings
Place catheters to encompass CTV.
Identify and demarcate normal structures that are at risk for complications
Reduce dose to critical normal structures
Place skin entry points of catheters at least 1 cm from the incision
Place catheters in parallel arrays at intervals of 1.0–1.5 cm
Secure catheters to avoid displacement
Load catheters no sooner than 5th day after wound closure when used as adjuvant monotherapy
Plan dosimetry with postoperative radiographs

CTV, clinical target volume.
Adapted from Nag S, et al. The American Brachytherapy Society recommendations for brachytherapy of soft tissue sarcomas. Int J Radiat Oncol Biol Phys. 2001;49(4):1033–1043.

Techniques

General techniques for BT using conventional sealed-end catheters, open-end catheters, and complex mesh implants are described in the subsequent text. Standard equipment used in the operating room for the sealed-end catheters and mesh implants are illustrated in Figures 10.2 and 10.3. A checklist of important steps in the preoperative planning, intraoperative execution, and postoperative management of BT for the surgical oncologist, radiation oncologist, reconstructive surgeon, nurses, operative room personnel, and hospital personnel is shown in Table 10.9. The steps in LDR implant placement and removal are outlined in Table 10.10. A comparison of the different modes of delivery of EBRT and BT is summarized in Table 10.11.

Sealed-End Catheter Technique

Principles

This technique can be used as boost or monotherapy for STS of the extremity, trunk, pelvis, retroperitoneum, and occasionally thorax (see Figs. 10.4, 10.5, 10.6, 10.7, 10.8, 10.9 and 10.10), using either LDR or HDR radiation. The afterloading catheter used is a flexible implant tube with single leader blind end (Fig. 10.2). The technique usually employs a single plane implant for R0 or R1 resection, although a double plane implant may be created after a R2 resection in the case of macroscopic residual disease.

Figure 10.2 Instruments used in sealed-end catheter implant: High dose rate catheters, trocar, spacer, and plastic buttons.

 

Figure 10.3 Instruments used in mesh implant: Needle driver, scissor, long forceps, 16-gauge angio-catheter needle, absorbable polyglactin 910 mesh, steel ring with 125I suture seeds, marker, and ruler.

Operative Course

After completion of resection, the surgical oncologist and radiation oncologist examine the resection specimen with the pathologist to evaluate margin status, using frozen section analysis if necessary. The surgical oncologist and radiation oncologist together examine the surgical bed to define the CTV. There is no consensus about the appropriate size of margin around the tumor bed that should be included in the treatment volume.47 The American Brachytherapy Society recommends at least a 1- to 2-cm margin laterally and a 2- to 5-cm margin longitudinally.47 Surgical clips are placed in the surgical bed to delineate the CTV and mark the critical structures.

A stainless steel trocar is inserted into the skin at least 1 cm away from the skin incision and is guided onto the tumor bed.26,32 The small gauge leader of the afterloading BT catheter is threaded through the trocar from the tumor bed to the exterior, and the trocar along with the BT catheter is pulled through the skin. The afterloading catheters are arranged in parallel and spaced 1 cm apart. Absorbable surgical sutures are used to secure the catheters to the tumor bed to prevent movement. Alternatively, catheters may be embedded in absorbable polyglactin 910 (Vicryl) woven mesh (Ethicon, Inc., Johnson & Johnson, Piscataway, NJ) to ensure parallel placement.64 Sutures are placed avoiding vital structures (nerve, vessels, ureter). A closed suction drain is placed and should be left until the end of treatment. After the surgical wound is closed, a plastic spacer is inserted onto each catheter at the skin surface, followed by a two-holed button. Although traditional buttons were made of metal, a plastic button is now available. The plastic button is magnetic resonance imaging (MRI) compatible and causes less image distortion in the CT images used for treatment planning. The buttons are sutured to the skin. Metallic buttons must be crimped to prevent any movement or slippage of the catheters; this must be done with caution to prevent damage to the catheter. The plastic buttons have a tighter fit to prevent catheter slippage. To minimize the risk of kinking the catheter while placing plastic buttons, the buttons are tested on a spare catheter. Each catheter is carefully identified for dosimetry planning. The exposed portion of the catheter as it emerges from the skin should be inked with a marker to facilitate identification of any catheter slippage. To prevent kinking of catheters before the loading of the isotopes (or in between treatments if using the HDR modality), a plastic or metallic guide wire should be inserted into each of the catheters. It is crucial to maintain sterility.

Table 10.9 Brachytherapy Planning Checklist

 

Mesh Implant

Catheter Implant LDR

Catheter Implant HDR

Preoperative Preparation

Surgical oncologist

Plan extent of resection necessary

Plan extent of resection necessary

Plan extent of resection necessary

Radiation oncologist

Dose range 0.25–0.60 Ci

LDR catheters

HDR catheters

 

Availability of 125I seed in strands

Extra catheters LDR trocar Buttons and spacers

Extra catheters HDR trocar Buttons and spacers

Reconstructive surgeon

Determine appropriate wound closure

Determine appropriate wound closure

Determine appropriate wound closure

Nurses/operating room personnel

Plan staffing to avoid exposure to pregnant personnel

N/A

N/A

Intraoperative Details

Surgical oncologist

Suture mesh implant without air pockets

Surgical clips to delineate CTV

Surgical clips to delineate CTV

 

Suture to avoid vital structures

Surgical clips to mark the critical structures

Surgical clips to mark the critical structures

 

Separate implant from structures as needed with Gelfoam, omentum, muscle flap

Secure catheters with suture or mesh

Secure catheters with suture or mesh

Radiation oncologist

Radiation survey upon entering the operating room

LDR catheters

HDR catheters

 

Inform personnel that radiation will be used

Trocar

Trocar

 

125I seeds in threads

Spacers

Spacers

 

Absorbable polyglactin 910 mesh

Buttons

Buttons

 

16-gauge angiocatheter needle

Suture buttons to skin

Suture buttons to skin

 

Marker

Leave guide wire in catheters

Leave guide wire in catheters

 

Ruler

 

 

 

Long forceps

 

 

 

Long needle driver

 

 

 

Surgical clips

 

 

 

Scissors

 

 

 

Radiation survey before leaving room

 

 

Reconstructive surgeon

Vascularized flap if applicable

Vascularized flap if applicable

Vascularized flap if applicable

 

 

Separate microvascular anastomosis from catheters

Separate microvascular anastomosis from catheters

Nurses/operating room personnel

Separate sterile setup for radiation oncologist

Separate sterile setup for radiation oncologist

Separate sterile setup for radiation oncologist

 

Allow pregnant personnel to leave

 

 

Postoperative Course

Surgical oncologist

Routine recovery course

Routine recovery course until postoperative day 5, then transfer to shielded room

Routine recovery course

 

 

Remove drain after treatment

Remove drain after treatment

Radiation oncologist

Plain radiographs and/or CT scans

Plain radiographs and/or CT scans

Plain radiographs and/or CT scans

 

Dosimetry

Dosimetry and planning

Dosimetry and planning

 

 

Order 192Ir ribbons

 

 

 

Start on fifth postoperative day or later

Start on fifth postoperative day or later

 

 

Check ribbons b.i.d

 

 

 

Available 24 h/d

 

Reconstructive surgeon

 

Remove drain after treatment

Remove drain after treatment

Nurses/hospital personnel

Low risk, but need to be informed

Stay behind lead shield

No restriction

 

 

Patient in isolated room

 

Family/visitors

If superficial, restrict holding infants/children

Restricted

No restriction

LDR, low dose rate; HDR, high dose rate; N/A, not applicable; CTV, clinical target volume.

Table 10.10 Low Dose Rate Brachytherapy Checklist for Postoperative Ribbon Loading and Removal

Loading Ribbons

Unloading Ribbons

1. Monitor room for radiation

2. Verify catheter position

3. Uncrimp buttons

4. Verify catheter patency

5. Bedside shield

6. Verify each 192Ir ribbon (radiation oncologist and physicist)

7. Long forceps for manipulation of ribbon

8. Crimp button

9. Confirm ribbon position (no slippage)

10.    Verify ribbon position twice daily

11.    Radiation oncologist must be available 24 h/d

1. Bedside shield

2. Uncrimp buttons

3. Long forceps to remove ribbon

4. Store removed ribbons in shield container

5. Monitor room for radiation

6. Remove button suture (sterile technique)

7. Remove catheter (sterile technique)

8. Compress to minimize bleeding

 

Table 10.11 Comparison of Treatment Delivery Options for External Beam Radiation Therapy and Brachytherapy

 

Preoperative Radiation Therapy

Postoperative Radiation Therapy

Permanent Mesh Implant 125I

Temporary Catheter Implant 192Ir

Start of treatment

Initial treatment, delays surgery

Delay, await postoperative recovery

No delay, intraoperative

Delay, >5 d postoperative

Duration of treatment

5 wk

6–7 wk

87 d (1.44 × half-life)

10–12 d

Volume irradiated

CTV with 5 cm-margin

5 cm margin for low-grade tumor, 7–10 cm for large and high grade, whole compartment

1–2 cm around CTV

Margin around CTV: 1–2 cm lateral, 2–5 cm longitudinal

Compartment irradiated (extremities)

No

Yes

No

No

Scar and drain irradiated

N/A

Yes

No

No

Normal tissue sparing

Yes

No

Yes

Yes

Final pathology and margin

Not available

Available

Not available

Available

Treatment completed upon discharge

Yes

No

Yes

Yes

Main advantages

Smaller operation and higher resectability

Tumor extent can be more clearly defined

Decrease radiation dose to normal tissue

Decrease radiation dose to normal tissue

N/A, not applicable.

Figure 10.4 Sealed-end catheter implant in situ after resection of a groin sarcoma. Catheter ends are seen entering the flank percutaneously well away from the incision. The internalized portions of the catheters are evenly spaced anterior to the left femoral artery. A closed suction drain enters away from the catheters.

 

Figure 10.5 Sealed end catheter implant after resection of a groin sarcoma. As the wound is closed, the catheters are secured to the skin with sutures through the plastic buttons.

Figure 10.6 A plain radiograph shows a posteroanterior view verifying the position of the radiopaque catheters after resection of a groin sarcoma.

 

Figure 10.7 Axial computed tomography reconstruction with catheters, clips, and isodose distributions.

 

Figure 10.8 Parasagittal computed tomography reconstruction with catheters, clips, and isodose distributions.

Postoperative Course

The patient's postoperative recovery, including antibiotic regimen, diet advancement, and activity, follows the usual course for the procedure performed and is managed by the surgical team(s). During this recovery period, the patient may stay in a standard ward or intensive care unit room.

Figure 10.9 Three-dimensional computer-generated image of dose cloud for high dose rate brachytherapy.

 

Figure 10.10 Three-dimensional computer-generated image of catheters and isodose lines after resection of a groin sarcoma, demonstrating excellent coverage of the clips with the prescription dose.

When the patient is stable to travel to the radiation oncology department, images for dosimetry are obtained. Traditionally, a set of three orthogonal plain films were taken for dosimetry, with dummy strands in each catheter (Fig. 10.6). However, this process of identifying each catheter was time consuming. More recently, the use of CT scan or MRI images has improved the quality of treatment planning and has facilitated catheter identification. CT- or MRI-compatible guides are inserted in each of the catheters. Images encompass the entire course of the catheters, from skin level to several centimeters beyond the distal end of the catheter. The image slice thickness should be no greater than 5 mm, permitting a 3D reconstruction of the catheter position and dose distribution (Figs. 10.7, 10.8, 10.9 and 10.10). Computer-based treatment planning has largely replaced manual planning. Isodose contour lines are determined. The radiation oncologist then selects the dose rate that adequately covers the CTV.

Treatment starts no earlier than the fifth postoperative day to limit wound toxicity.51 Catheter loading may be delayed by 1 to 2 days if there are concerns about the wound; the technique for LDR and HDR differ henceforth. For LDR BT, the patient is transferred to a shielded lined hospital room. The isotope ribbons, corresponding to specific catheters, are stored in a lead-lined container after delivery by overnight courier. At the minimum, two providers (the radiation oncologist and either a physicist or a radiation safety officer) are needed to load the ribbons. First, the room is monitored for any radiation. Second, the positions of the catheters are verified, and metallic buttons (if present) are uncrimped. The patency of each catheter is confirmed with a guide wire. Third, bedside shielding is placed to protect all personnel. Fourth, ribbons are inserted using long forceps. Each ribbon should be identified when handed to the radiation oncologist, who in turn should also identify and confirm into which catheter the ribbon is inserted. The buttons are carefully crimped and each ribbon is reevaluated for potential slippage. Fifth, a radiation reading of the room is taken. Finally, during the course of treatment, the ribbons and catheters are verified twice a day to identify any slippage and evaluate for any signs of infection.

The BT radiation oncologist should be available at all times during treatment should problems arise. All hospital personnel involved in the patient's care must be in-serviced and educated to avoid inappropriate or unnecessary exposure. See Chapter 2 for detailed radiation safety procedures and equipments.

Treatment course terminates as specified by the dosimetry. As before, two providers are needed to remove the ribbons and catheters. First, the buttons are uncrimped and the ribbons are removed with long forceps and placed in a lead-lined container. Second, a radiation survey of the patient and the room is performed to confirm that there are no residual radiation sources. Third, with sterile technique the catheter sutures are removed, and each catheter is extracted. This must be performed with great care to avoid significant complications, particularly when the catheters are adjacent to neurovascular structures, vascular anastomoses, or flap reconstructions. Minimal pain or bleeding may be expected; sterile gauze may be used for compression.

Although the principles are the same for HDR BT, a shielded inpatient room is not needed. HDR afterloaded fractionated postoperative therapy allows quicker discharge from the hospital and the patient can attend once- or twice-daily treatments as an outpatient. Wise use of slings, knee immobilizers, and bandages minimizes the risk of dislodging catheters before therapy is complete. Instead, the fractionated treatment is administered in the radiation oncology department where the HDR afterloader is used in a shielded treatment room. The catheters are connected to individual cables, which in turn are connected to the HDR afterloader. Importantly, the attachment is not random; rather, it is determined by pretreatment dosimetric/physics planning. There is no limit to the number of catheters for this modality. Each of the commercially available afterloaders has a limit on the number of catheters per treatment session. If the total number is higher than the limit, then a second session is created from the same treatment plan. A single high activity (nominal activity of 10 Ci) 192Ir source will travel in each catheter and will stop at each dwell position for a unique time that is specified by the computer-optimized plan and controlled by computer guidance.

When using both techniques in the same institution, HDR catheters may be used for both types of implant to minimize error. HDR catheters can accommodate LDR 192Ir ribbons, but LDR catheters cannot accommodate the HDR 192Ir source because the hubs, adapters, and transfer tubes are unique to each afterloader system. Other details about catheter management are the same for both techniques.

Figure 10.11 Vicryl mesh implant. 125I seeds embedded in vicryl sutane (purple) are evenly positioned in the absorbable mesh. Titanium clips secure the strands into position.

 

Open-End Catheter Technique

Principles

This technique is mainly used in head and neck or breast tumors. It employs an LDR implant with 192Ir ribbons. Catheter placement, spacing, immobilization, and CTV margin coverage are identical to the sealed-end catheter technique. However, both ends of each catheter exit the skin. There is an increased risk of fluid entering the catheters, potentially interfering with the isotope ribbons. There is also an increased possibility of isotope loss. At present, this is not the preferred BT technique in STS.

Mesh Implant Technique

Principles

A permanent mesh implant is a single plane implant using 125I seeds. This mesh technique has been described in the management of stage I non–small-cell lung carcinoma.65 In contrast to 192Ir, the isotope 125I has a short range of penetration ideally targeted at microscopic residual disease (i.e., after an R1 resection). Mesh implants may be used for monotherapy or boost treatment in conjunction with EBRT (see Figs. 10.11, 10.12 and 10.13).

The 125I seeds are embedded in suture strands (energy range, 0.25 to 0.60 Ci). Each strand is secured to a curved surgical needle and contains 10 seeds each 1 cm apart (Fig. 10.3). Each strand is individually packed in a stainless steel ring.

The mesh technique offers several advantages over the traditional catheter technique (see Table 10.12). A mesh is more flexible and may therefore be placed in anatomic sites difficult to access (see Figs. 10.14 and 10.15). There are no catheters protruding from the wound. The radiation treatment starts immediately, in comparison to a delay of 5 or more days in a conventional catheter implant. Owing to the short range of penetration of 125I, there is less exposure for the hospital personnel.

There is little published experience to date with the mesh implant embedded with 125I seeds. At present, there is no consensus about the maximum size of implant that may be safely and effectively used.

Figure 10.12 125I mesh implant in situ after resection of a forearm sarcoma.

 

Figure 10.13 A plain radiograph shows a posteroanterior view verifying the position of the radiopaque seeds linearly separated by 1 cm after resection of a forearm sarcoma.

Operative Course

As in the catheter technique, the surgical oncologist and radiation oncologist examine the resection specimen and define the CTV. Careful measurement of the area is mandatory. A 1-cm margin should be added to the tumor bed dimensions. On a sterile, rectangular, absorbable polyglactin 910 (Vicryl) woven mesh (or occasionally nonabsorbable polypropylene mesh), the CTV is delineated with a marker. The seeds embedded in suture are threaded into the mesh evenly spaced, with usually 1 cm separating each strand (depending on the energy of the isotope). Nomograms have been developed for single and double plane implant as a guide for the distance between strands of isotopes (see Chapter 6). To help thread the strands into the mesh and to limit the risk of a seed slipping from the strand, a 16-gauge angiocatheter needle may be used to create holes in the mesh. Although penetration of the 125I isotope is minimal, a long needle driver and long forceps are used to manipulate the implant to limit exposure to the hands. After each strand has been threaded in the mesh, the suture needle is removed and the strand is secured with surgical clips at both ends to prevent slippage (Fig. 10.11). Excess mesh may be trimmed away. Therefore, each implant is custom-made. The surgical oncologist lays the mesh implant over the previously determined CTV and, together with the radiation oncologist, sutures it into place. Sutures are placed to avoid vital structures (vessels, ureter, and whenever possible, nerves). A crucial aspect of this technique is that the implant must make full contact with the tumor bed; given the rapid fall-off of the 125I isotope, there should be no air pockets (Fig. 10.12). Arteries, including the aorta, should be buttressed with viable tissue (omentum, muscle flap) or absorbable material (Gelfoam, Pharmacia & Upjohn Company, Kalamazoo, MI) to minimize the risk of aneurysmal dilatation. The wound is closed in the standard fashion.

Table 10.12 Advantages of the Mesh-Based Technique Over the Catheter-Based Technique for Administration of Brachytherapy

More flexible and more easily contoured to tumor bed
No ends of catheters protruding from wounds
A more immediate treatment of wound bed while still well vascularized and not scarred
Minimal exposure for staff
Shorter hospital stay

Figure 10.14 A plain radiograph shows a posteroanterior view verifying the position of the radiopaque 125I seeds after resection of a pelvic sarcoma.

 

Figure 10.15 Three-dimensional computed tomography image reconstruction of a thoracic 125I seed implant.

Postoperative Course

The patient's postoperative recovery follows the usual course for the procedure performed and is managed by the surgical team(s). Throughout the recovery period until discharge, the patient may stay in standard ward or intensive care unit rooms. The nursing staff should be aware of the implant, as pregnant women should avoid contact with the patient to minimize potential dose to the fetus. When the patient is stable to travel to the radiation oncology department, images for dosimetry are obtained.

Plain radiographs and a CT scan of the site are obtained before discharge (Figs. 10.7, 10.8, 10.9 and 10.10 and 10.13 and 10.14). CT reconstruction of the seed location is performed. A radiation dosimetrist or physicist will perform the necessary calculations, and a final dosimetric plan will be placed in the patient's chart.

The patient is discharged from the hospital after standard recovery. No additional hospitalization for BT treatment is required. Should there be any children or pregnant women in the patient's household, additional radiation measures with a survey meter will be performed at the skin surface and at a 1-m distance from the patient. The radiation safety officer of the hospital will be consulted and recommendations provided to the patient (see Chapter 2).

Dose of Radiation

The dose selection effective in treating STS evolved from a seminal study from the Massachusetts General Hospital. Fifty-one patients with STS were treated with radiation alone.66 The 5-year local control and OS rates were 33% and 25%, respectively, for total doses <64 Gy, and 44% and 28% for doses >64 Gy.

Low Dose Rate

The dose rate of radiation using 192Ir plastic ribbons is 40 to 100 cGy per hour. Ribbons may be custom-made to fit the treatment. The sources are 0.5 mg of radium equivalent at every centimeter. Each source is 4-mm long; the number of sources per ribbon is variable. The maximum number of sources per ribbon is 18. Iridium sources are ordered 24 hours before use. 125I is available as either a loose seed or a strand of 10 seeds spaced 1 cm apart (see Chapters 4 and 12).

High Dose Rate

The high dose rate of radiation is >1200 cGy per hour. Because of the difference in dose rate between LDR and HDR, the dose is not equivalent between these two modalities. Dose equivalence must be determined by the physicist. The total dose for HDR will be lower than that for LDR to have the equivalent radiobiologic effect in tissue. HDR afterloaders use a single 192Ir source laser-welded to the end of a flexible stainless steel cable. Up to 18 catheters may be attached to the afterloader at a time. The computer-guided afterloader directs the source in each catheter. This source is replaced every 3 months. A new source has a strength of 10 Ci; with radioactive decay, the strength is 4 Ci after 3 months. Treatment is delivered twice daily over 4 to 5 days, with a minimum gap of 6 hours between treatments to allow for sufficient repairs of sublethal damage in normal tissues.

 

Table 10.13 Treatment Doses

 

Dose

Days of Administration

Other

LDR monotherapy

45–50 Gy

4–6

Iso-equivalent to EBRT

LDR boost therapy combined with EBRT

15–25 Gy (40–50 cGy/h)

2–3

Combined with EBRT 45–50 Gy

HDR

3,400 cGy/10 fraction

5

No consensus

LDR in recurrent disease

45–50 Gy (40–50 cGy/h)

4–6

Adjust on the basis of prior radiation therapy and OAR

HDR in recurrent disease

Up to 3,400 cGy/10 fraction

5

Adjust on the basis of prior radiation therapy and OAR

LDR, low dose rate; HDR, high dose rate; EBRT, external beam radiation therapy; OAR, organs at risk.

HDR BT has several advantages over LDR. There is potentially a better dose distribution. The source travels in each catheter in a stepwise fashion to specified dwell positions. The time that the source stays at each dwell position may be controlled, enabling the dose distribution to be modulated. A 3D reconstruction of the catheter position using CT scan or MRI images is added for treatment planning for greater precision.

Treatment Doses

Recommended treatment doses are outlined in Table 10.13.

Special Situations

Extremity Sarcoma

Treatment of extremity STS is one of the most common indications for BT. Extremity tumors account for 46% of all sarcomas (14% are upper extremity, 32% are lower extremity).3 Tissue and function preservation are important outcomes in evaluating the impact of RT in extremity STS. Experience with EBRT has confirmed that, when the total circumference of an extremity is irradiated, tissue fibrosis and scarring subsequently impair limb function. An implant, with the short range of penetration of the isotopes, is appealing at this site in an effort to permit tissue sparing. As the implant increases in size, the benefit of geometric sparing diminishes, as volume covered resembles that of an external beam treatment.

Special care is warranted when an implant crosses a joint. If the implant is not appropriately sutured to the target volume, movement at the joint may displace the implant or kink the catheters. If this is suspected, new radiographic images must be obtained. Immobilization is essential for the duration of the implant.

Thoracic Sarcoma

Thoracic STS account for 17% of all sarcomas. The unique anatomy of the thorax makes catheter placement awkward, although if the tumor is superficial, this technique may be used. Hence, mesh implants can be more amenable for this location, as they are flexible. The long-term sequelae on surrounding vital structures, including the heart and great vessels, are unknown, so BT must be used with caution (see Chapter 6 for the technique).

Retroperitoneal Sarcoma

Retroperitoneal sarcomas account for 12% of all sarcomas and pose distinct challenges. Local recurrences remain high, >50%, despite R0/R1 resection with removal of multiple organs.67 The proximity of radiosensitive structures, including the kidney, liver, stomach, and bowel, limit the delivery of EBRT.

In a prospective randomized trial from the NCI, intraoperative radiation therapy (IORT) combined with EBRT resulted in improved local control compared with EBRT alone, with no difference in median survival times.68 Such results stimulated interest in developing alternative delivery systems for IORT. The HDR remote afterloader used for BT has been combined with an intraoperative applicator to deliver radiation customized to the tumor bed with other organs retracted out of the field.69

Jones et al. reported the experience of the University of Toronto with 46 patients with primary or locally recurrent retroperitoneal sarcomas (RPS) resected for cure and treated with preoperative EBRT (41 patients) and/or BT (23 patients).35 With a median follow-up of 19 months, local recurrences were identified in 9 (20%) of 46 patients; one (2%) additional patient developed both local and distant recurrences. The 2-year DFS and OS rates were 80% and 88%, respectively. Survival data were not stratified by the presence or absence of BT. BT to the upper abdomen was associated with significant toxicities. In particular, there were two late deaths from duodenal perforation during placement of feeding tubes for duodenal strictures secondary to BT. This study showed that (a) local control rates for RPS were acceptable with the administration of BT, but (b) the treatment was associated with severe upper abdominal toxicities, prompting a change in the authors' protocol, limiting BT to lower abdominal tumors.

Desmoid Tumors

Desmoid tumors present a unique problem in sarcoma therapy. Although these tumors have low malignant potential, they may be locally very aggressive. Zelefsky et al. reported the cumulative MSKCC experience with these tumors treated with surgery and RT, largely BT.70 Despite having unfavorable features (75% were recurrent, 16% had gross residual disease), local control was achieved in 66% of cases. One third of local failures occurred at the periphery of the implanted volume. This study recommended that BT implants should only be used as adjuvant boost therapy (20 to 25 Gy) with supplemental EBRT (45 to 50 Gy) to more appropriately cover the target volume.

Kaposi Sarcoma

Kaposi sarcoma (KS) is a multicentric superficial vascular proliferation with a purple coloration with a propensity to occur in the extremities.71 There are three common recognized types. Classic KS is seen most commonly in Ashkenazi Jews or in Mediterranean populations. Endemic KS is a more aggressive form predominantly seen in Africa. This form affects a younger age group and frequent involves regional lymph nodes. Human immunodeficiency virus-related KS is associated with human herpes virus 8.71

In general, treatment commences with antiretroviral therapy or chemotherapy, depending on the extent of disease and CD4 counts.71 BT may be use to control limited cutaneous disease or palliate painful lesions. A surface applicator consisting of flexible flaps with multiple channels spaced 1 cm apart is utilized. Such an applicator offers the advantage, over external beam therapy, of conforming to a limb or a more rounded body part. It is placed directly on the skin over the carefully isolated lesion. An Aquaplast cast assures reproducibility of the position. CT-compatible guide wires are placed in the chosen channels, which are then documented. A margin of 1 cm is given around the lesion and the dose prescribed to the surface. A single 600-cGy fraction may be employed for palliation; alternatively, multiple smaller fractions over a week or two may be more suitable.

Positive Margins

Positive margins present a challenging oncologic problem. To treat the margin, neither BT nor EBRT is optimal as a stand-alone therapy; the field is larger than what BT can cover, and the dose of radiation necessary is greater than what EBRT can provide. Instead, EBRT (45 to 50 Gy) combined with boost BT (15 to 20 Gy) may provide adequate coverage. Although such radiation modalities may provide adjuvant therapy to improve local control, neither is more effective than an adequate margin-negative resection.

Previously Irradiated Field

Pearlstone et al. from M. D. Anderson Cancer Center (MDACC) reported their experience with patients with previously irradiated STS who underwent BT for their recurrence.72 Twenty-six patients with recurrent STS previously treated with a mean EBRT dose of 55.6 Gy were reirradiated with BT at a mean dose of 47.2 Gy. The 5-year local recurrence-free survival was 52% for all patients and was 29% in the 17 patients with extremity lesions. Complications were identified in 19% of the patients and included wound breakdown, osteonecrosis, and neuralgia.

Nori et al. from MSKCC treated 40 previously irradiated patients with recurrent sarcoma with a median BT dose of 45 Gy.73 They reported an actuarial 5-year local control rate of 69%. The 5-year actuarial OS rates were 85% for one to two recurrences versus 55% for three or more recurrences. Complications were reported in 12.5% of the patients and included ulceration and femoral fracture.

Catton et al. from the Princess Margaret Hospital reported a series of patients with locally recurrent, previously irradiated extremity STS treated with salvage therapy.74 In this study, 7 patients were not candidates for conservative reexcision and underwent amputation, 11 underwent local excision alone, and 10 were treated with resection and reirradiation (6 BT alone, 3 EBRT alone, and 1 both BT and EBRT). At a median follow-up of 24 months, the local control rates were 36% for local excision alone and 100% for resection and reirradiation in 10 pts with prior surgery and radiation. Complete local control (100%) was seen at median 24 months follow up. Significant wound healing complications were seen in 60% of patients in the reirradiation group, but ultimately, 70% had good to excellent posttreatment function scores. Therefore, combined reexcision and reirradiation had superior local control compared with local excision alone and superior function compared with amputation.

Low-Grade Sarcomas

It is uncertain why patients with low-grade tumors do not benefit from BT. It is possible that because of the relatively small sample size of patients with low-grade tumors no statistically significant benefit is seen. Alternatively, as low-grade lesions progress through cell cycle at a rate slower than high-grade lesions, the 4- to 6-day treatment time of the implant may be too short to catch all cells in a radiosensitive phase of the cell cycle. Nevertheless, on the basis of present evidence, EBRT may provide some benefit for low-grade tumors, whereas BT does not, except perhaps in the setting of recurrence.

Quality of Life

Conservative surgery and adjuvant therapy have increased limb and function preservation and improved the quality of life. Adjuvant therapy, in particular radiation, may impact limb function. As described earlier, total dosage must be carefully monitored to prevent late complications such as fibrosis and neuropathy.

Intraoperative Radiation Therapy Versus Brachytherapy

The goal of both BT and IORT is to safely administer a high local dose of radiation to the CTV while protecting the adjacent normal and the critical structure. The total dose provided would be prohibitive if administered by EBRT alone. Special expertise is needed for each technique and knowledge of the specific anatomy is mandatory.

IORT usually employs electrons of different energy, although some facilities have orthovoltage radiation. IORT is a single fraction treatment with a typical dose range of 10 to 20 Gy.


It may be used as boost therapy (i.e., in recurrent disease) or occasionally as monotherapy. Most centers use a modified linear accelerator for generating electrons, with energy ranges from 6 to 21 MeV. Applicators or “cones” of different sizes with beveled ends are used to deliver the radiation. These applicators are attached to the linear accelerator and are chosen intraoperatively. Distinct advantages of IORT are the ability to deliver a homogeneous dose and direct visualization of the tumor volume (for a better assessment of the CTV).

The choice between these two techniques is related to the expertise of the physician, the equipment available, and the ability to safely administer the treatment while sparing the critical structures. IORT, with its single high dose of radiation, is less forgiving if administered to a critical structure. Therefore, with IORT, vital structures must be moved out of the path of the single dose fraction. In contrast, with BT, irradiation of uninvolved critical structures may be minimized by the interposition of spacing agents such as Gelfoam (Pharmacia & Upjohn Company, Kalamazoo, MI), muscle flap, omentum, and so on.

The studies reviewed above demonstrate improved local control with BT. Similarly, in trials comparing IORT in conjunction with low-dose postoperative EBRT to high-dose EBRT alone, patients in the IORT arm experienced improved local control and fewer cases of radiation enteritis, but had more cases of peripheral neuropathy.68 IORT may provide survival benefit as well.75

Future Directions

Intensity-modulated radiation therapy (IMRT) is a form of external beam radiation that permits more precision in the delivery of radiation to a specific tumor volume. The treatment is optimized by sophisticated computer software. With this technique, margins are set tighter, sparing more volume of normal tissue. Furthermore, higher total doses are usually possible. The rationale is better local tumor control while sparing adjacent normal tissue. At present, it has not replaced the combination of BT and EBRT in the treatment of sarcoma. As with EBRT, dose limiting toxicity of normal structures still remains a limitation of this technique. Another limitation is the risk of geographical miss when the margins are set too close to the CTV, in the context of internal organ movement.

Biologic interventions such as immunotherapy (vaccines, monoclonal antibodies) and in gene therapy are some of the new approaches being studied in the treatment of advanced and recurrent sarcomas. Many years of intense research are still needed before these approaches can make an impact.

Conclusions

Perioperative BT results in a better local control rate than surgery alone for certain extremity STS. There is no firm evidence that BT is superior to EBRT in high-grade lesions. No prospective trials have compared these two treatment modalities. BT does not improve local control in low-grade lesions. BT is highly effective in controlling high-grade tumors, independent of size, location in the extremity, and depth. However, it does not prevent the development of distant metastases or prolong survival even in high-grade tumors. It remains to be seen whether adjuvant chemotherapy improves the survival numbers of patients with sarcoma treated with surgery and BT, with or without EBRT. Acute wound complication rates may be reduced by not loading the implant earlier than the fifth postoperative day. Late effects such as neurotoxicity from implant placement near critical nerves may be minimized by keeping the total radiation dose below 90 Gy. Long bone fracture rates depend on whether a portion of the bone or periosteum is resected.

Acknowledgments

We would like to thank Desmond A. O'Farrell, CMD, Jorgen L. Hansen and Robert Cormack Ph.D. for dosimetric images, 3D reconstruction, and postoperative verification films, Jorgen L. Hansen, M.S. for instrument images and photography expertise, and Alexandra J. Stewart, BM, MRCP and Subhakar Mutyala, M.D. for intraoperative images.

Chapter 10 Case Studies

Case 1

A 46-year-old woman presented with liposarcoma of the left popliteal fossa. She underwent neoadjuvant chemoradiation with doxorubicin and ifosfamide and 50 Gy of EBRT. After marginal resection, the tumor bed was marked with clips and covered with four sealed-end HDR catheters. After complex computer-optimized CT simulation, a hyperfractionated HDR BT treatment course of 375 cGy twice daily for 8 fractions (total 30 Gy) was prescribed. The surgical clips were covered with the 100% isodose line (see Figs. 10.1610.1710.1810.1910.20 and 10.21).

Case 2

A 63-year-old woman presented with recurrent perinephric liposarcoma along the superior medial aspect of the left kidney. It is of note that she had previously undergone a right nephrectomy for transitional cell carcinoma. Resection required removal of the renal capsule en bloc with the tumor, the spleen, left adrenal gland and a portion of the left hemidiaphragm. Although all gross disease was removed, the tumor abutted the renal capsule without invading it. Nevertheless, the margin was only 1 to 2 mm. To achieve the goal of local tumor control with preservation of kidney function, a mesh implant measuring 9 × 5 cm was designed to cover the area at risk. Five strands of 125I (0.263 mCi per seed) were incorporated into the mesh spaced 1 cm apart. Postoperative dosimetry demonstrated that a dose of 75 Gy (very low dose rate [VLDR]) was delivered to a very conformal target and that most of the kidney was under known tolerance. The dose–volume histogram for the kidney was a V10 of 29% and a V30 of 5.6% (see Figs. 10.2210.23 and 10.24)

Figure 10.16 Resection of the liposarcoma. The tumor closely abutted popliteal nerve and artery. These were not directly involved in the tumor and were fastidiously dissected from the tumor capsule.

Figure 10.17 Excised liposarcoma with previous biopsy skin wound excised en bloc.

 

Case 3

An 86-year-old woman presented with recurrent Mediterranean Kaposi Sarcoma of the lower extremity. She had previously received palliative EBRT with 30 Gy photons and 10 Gy of electron boost. Despite this aggressive therapy, her lesions were persistent and quite painful. Customized surface applicators were used for the dorsum of her right foot and right posterior calf (see Figs. 10.2510.2610.27 and 10.28). A single fraction of 600 cGy to each site provided significant palliation. It is of note that large surface areas take up significant treatment time—running into hours when the surface area is large and the isotope is toward the lower end of its activity. This is may not be well tolerated by either the patient, the staff or the clinic setup.

Figure 10.18 Insertion of the trocar through the skin. It is important not to be too close to the edge of the wound so as not to compromise blood flow as the wound heals. The trocar is advanced under direct visualization. The use of an inked line ensures the catheters enter 1 cm apart. Care should be taken not to inadvertently tattoo the skin by passing the trocar directly through the ink line.

Figure 10.19 The catheter is threaded through the trocar. The thin catheter leader is brought out through the wound in a retrograde direction so that the hollow catheter is correctly placed. Care must be taken not to kink, cut, or puncture the catheters.

 

Figure 10.20 Buttons are used to secure the catheters to the skin. A variety of buttons are used. Nonmetallic buttons minimize scatter during computed tomography. The buttons are stitched to the skin with small gauge nylon sutures at the end of the case.

Figure 10.21 A view of the catheters with buttons secured onto the tumor bed. The catheters are carefully affixed to the deep margin with interrupted chromic gut suture. The surgeon and the radiation oncologist guard against inadvertent puncture of vessels, nerves, or the catheters. The spacing reflects how the wound will come together at closure. Fewer catheters may be achievable as some of the target area will be folded over the catheters when the wound is closed. Manual approximation of the wound assists in this evaluation.

 

Figure 10.22 Retroperitoneal sarcoma implantation at superior pole of left kidney for positive margin. Axial image, with isodose lines and relationship of implant with kidney are shown.

Figure 10.23 Coronal image showing isodose lines and relationship of implant with kidney.

 

Figure 10.24 Sagittal image showing isodose lines and relationship of implant with kidney.

Figure 10.25 Clinical presentation of recurrent and symptomatic Mediterranean Kaposi Sarcoma on dorsum of foot that had previously received palliative external beam radiation of 3,000 cGy in 10 fractions.

 

Figure 10.26 A customized surface applicator is fashioned to fit snugly to the clinical target area that is mapped out with computed tomography marker wire. Copper dummy strands aid in treatment planning.

Figure 10.27 A computed tomography computer-optimized isodose plan shows perfect conformance of 100% isodose to the clinical target area with excellent sparing of deep tissues.

 

Figure 10.28 The same patient also had a symptomatic large flat area on the calf, which was treated in an analogous manner.

 

References

1. Rosenberg SA, Tepper J, Glatstein E, et al. Prospective randomized evaluation of adjuvant chemotherapy in adults with soft tissue sarcomas of the extremities. Cancer. 1983;52:424–434.

2. Shiu MH, Costro EB, Hajdu SI, et al. Surgical treatment of 297 soft tissue sarcomas of the lower extremity. Ann Surg. 1975;182(5):597–602.

3. Brennan MF, Alektiar KM, Maki RG. Sarcomas of the soft tissue and bone. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: Principles and practice of oncology. Philadelphia, PA: Lippincott Williams & Wilkins; 2001:1841–1935.

4. Suit H, Spiro I. Radiation as a therapeutic modality in sarcomas of the soft tissue. Hematol Oncol Clin North Am. 1995;9(4):733–746.

5. Habrand JL, Le Pechoux C. Radiation therapy in the management of adult soft tissue sarcomas. Ann Oncol. 2004;15(Suppl 4):4187–4191.

6. Tepper JE, Suit HD. The role of radiation therapy in the treatment of sarcoma of soft tissue. Cancer Invest. 1985;3(6):587–592.

7. 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 therapy compared with amputation and (2) the role of adjuvant chemotherapy. Ann Surg. 1982;196(3):305–315.

8. Yang JC, Chang AE, Baker AR, et al. Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity. J Clin Oncol. 1998;16(1):197–203.

9. Pollack A, Zagars GK, Goswitz MS, et al. Preoperative vs. postoperative radiotherapy in the treatment of soft tissue sarcomas: a matter of presentation. Int J Radiat Oncol Biol Phys. 1998;42(3):563–572.

10. Henschke UK, Hilaris BS, Mahan GD. Afterloading in interstitial and intracavitary radiation therapy. Am J Roentgenol Radium Ther Nucl Med. 1963;90:386–395.

11. Collins JE, Paine CH, Ellis F. Treatment of connective tissue sarcomas by local excision followed by radioactive implant. Clin Radiol. 1976;27(1):39–41.

12. Ellis F, Connective tissue sarcomata. In: Handbook of interstitial brachytherapy. Hilaris BS, eds. Acton, MA: Publishing Sciences Group; 1975:263–273.

13. Janjan NA, Yasko AW, Reece GP, et al. Comparison of charges related to radiotherapy for soft-tissue sarcomas treated by preoperative external-beam irradiation versus interstitial implantation. Ann Surg Oncol. 1994;1(5):415–422.

14. Harrison LB, Franzese F, Gaynor JJ, et al. Long-term results of a prospective randomized trial of adjuvant brachytherapy in the management of completely resected soft tissue sarcomas of the extremity and superficial trunk. Int J Radiat Oncol Biol Phys. 1993;27(2):259–265.

15. Delaney TF, Trofimov AV, Engelsman M, et al. Advanced-technology radiation therapy in the management of bone and soft tissue sarcomas. Cancer Control. 2005;12(1):27–35.

16. Ballo MT, Lee AK. Current results of brachytherapy for soft tissue sarcoma. Curr Opin Oncol. 2003;15(4):313–318.

17. Habrand JL, Gerbaulet A, Pejovic MH, et al. Twenty years experience of interstitial iridium brachytherapy in the management of soft tissue sarcomas. Int J Radiat Oncol Biol Phys. 1991;20(3):405–411.

18. Brennan MF, Hilaris B, Shiu MH, et al. Local recurrence in adult soft-tissue sarcoma. A randomized trial of brachytherapy. Arch Surg. 1987;122(11):1289–1293.

19. Pisters PW, Harrison LB, Leung DH, et al. Long-term results of a prospective randomized trial of adjuvant brachytherapy in soft tissue sarcoma. J Clin Oncol. 1996;14(3):859–868.

20. Tanabe KK, Pollock RE, Ellis LM, et al. Influence of surgical margins on outcome in patients with preoperatively irradiated extremity soft tissue sarcomas. Cancer. 1994;73(6):1652–1659.

21. Alektiar KM, Leung D, Zelefsky MJ, et al. Adjuvant brachytherapy for primary high-grade soft tissue sarcoma of the extremity. Ann Surg Oncol. 2002;9(1):48–56.

22. Brown FM, Fletcher CD. Problems in grading soft tissue sarcomas. Am J Clin Pathol. 2000;114(1 Suppl 1):S82–S89.

23. Hilaris BS. Limb-sparing therapy for locally advanced soft-tissue sarcoma. Endocuriether/Hyperther Oncol. 1985;1:17–24.

24. Shiu MH, Turnbull AD, Nori D, et al. Control of locally advanced extremity soft tissue sarcomas by function-saving resection and brachytherapy. Cancer. 1984;53(6):1385–1392.

25. Zelefsky MJ, Nori D, Shiu MH, et al. Limb salvage in soft tissue sarcomas involving neurovascular structures using combined surgical resection and brachytherapy. Int J Radiat Oncol Biol Phys. 1990;19(4):913–918.

26. Chaudhary AJ, Laskar S, Badhwar R. Interstitial brachytherapy in soft tissue sarcomas. The Tata Memorial Hospital experience. Strahlenther Onkol. 1998;174(10):522–528.

27. Mills EE, Hering ER. Management of soft tissue tumours by limited surgery combined with tumour bed irradiation using brachytherapy and supplementary teletherapy. Br J Radiol. 1981;54(640):312–317.

28. Schray MF, Gunderson LL, Sim FH, et al. Soft tissue sarcoma. Integration of brachytherapy, resection, and external irradiation. Cancer. 1990;66(3):451–456.

29. Gemer LS, Trowbridge DR, Neff J, et al. Local recurrence of soft tissue sarcoma following brachytherapy. Int J Radiat Oncol Biol Phys. 1991;20(3):587–592.

30. Cionini L, Marzano S, Olmi P. Soft tissue sarcomas: experience with intraoperative brachytherapy in the conservative management. Ann Oncol. 1992;3(Suppl 2):S63–S66.

31. O'Connor MI, Pritchard DJ, Gunderson LL. Integration of limb-sparing surgery, brachytherapy, and external-beam irradiation in the treatment of soft-tissue sarcomas. Clin Orthop Relat Res. 1993;(289):73–80.

32. Burmeister BH, Dickinson I, Bryant G, et al. Intra-operative implant brachytherapy in the management of soft-tissue sarcomas. Aust N Z J Surg. 1997;67(1):5–8.

33. Dellanes M. Low dose rate intraoperative brachytherapy for soft tissue sarcomas: 85 case reports [Abstract]. Radiother Oncol. 1996;39(Suppl 1):S3.

34. Rosenblatt E, Meushar N, Bar-Deroma R, et al. Interstitial brachytherapy in soft tissue sarcomas: the Rambam experience. Isr Med Assoc J. 2003;5(8):547–551.

35. Jones JJ, Catton CN, BO'Sullivan, et al. Initial results of a trial of preoperative external-beam radiation therapy and postoperative brachytherapy for retroperitoneal sarcoma. Ann Surg Oncol. 2002;9(4):346–354.

36. Shiu MH, Hilaris BS, Harrison LB, et al. Brachytherapy and function-saving resection of soft tissue sarcoma arising in the limb. Int J Radiat Oncol Biol Phys. 1991;21(6):1485–1492.

37. Pisters PW, Harrison LB, Woodruff JM, et al. A prospective randomized trial of adjuvant brachytherapy in the management of low-grade soft tissue sarcomas of the extremity and superficial trunk. J Clin Oncol. 1994;12(6):1150–1155.

38. Brennan MF, Caspar ES, Harrison LB, et al. The role of multimodality therapy in soft-tissue sarcoma. Ann Surg. 1991;214(3):328–336 discussion 336–338.

39. Schupak KD. The psychofunctional handicap associated with the use of brachytherapy in the treatment of lower extremity high grade soft tissue sarcomas. Int J Radiat Oncol Biol Phys. 1993;27(12):1567–1574.

40. Alektiar KM. Preliminary results of hyper-fractionated high dose rate brachytherapy in soft-tissue sarcomas. Endocuriether/Hyperther Oncol. 1994;10:179–184.

41. Koizumi M, Inove T, Yamazaki H, et al. Perioperative fractionated high-dose rate brachytherapy for malignant bone and soft tissue tumors. Int J Radiat Oncol Biol Phys. 1999;43(5):989–993.

42. Chun M, Kang S, Kim BS, et al. High dose rate interstitial brachytherapy in soft tissue sarcoma: technical aspects and results. Jpn J Clin Oncol. 2001;31(6):279–283.

43. Chuba R. Adjuvant brachytherapy for primary and recurrent soft tissue sarcoma at WSU [Abstract]. Radiother Oncol. 1996;39(Suppl 1):S4.

44. Crownover RL, Marks KE, Zehr RJ. Initial results with high dose rate brachytherapy for soft-tissue sarcomas. Sarcoma. 1997;1:196–205.

45. Donath D. Postoperative adjuvant high dose rate brachytherapy in the treatment of poor prognosis soft tissue sarcoma [Abstract]. Endocuriether/Hyperther Oncol. 1993;9:48.

46. Yoshida K. Perioperative high dose rate brachytherapy for bone and soft tissue tumors. Nippon Acta Radiologica (Tokyo). 1996;41:1635–1641.

47. Nag S, Shasha D, Janjan N, et al. The American Brachytherapy Society recommendations for brachytherapy of soft tissue sarcomas. Int J Radiat Oncol Biol Phys. 2001;49(4):1033–1043.

48. Lindberg RD, Martin RG, Romsdahl MM, et al. Conservative surgery and postoperative radiotherapy in 300 adults with soft-tissue sarcomas. Cancer. 1981;47(10):2391–2397.

49. Rosenberg SA, Glatstein EJ. Perspectives on the role of surgery and radiation therapy in the treatment of soft tissue sarcomas of the extremities. Semin Oncol. 1981;8(2):190–200.

50. Suit HD, Mankin HJ, Wood WC, et al. Preoperative, intraoperative, and postoperative radiation in the treatment of primary soft tissue sarcoma. Cancer. 1985;55(11):2659–2667.

51. Arbeit JM, Hilaris BS, Brennan MF. Wound complications in the multimodality treatment of extremity and superficial truncal sarcomas. J Clin Oncol. 1987;5(3):480–488.

52. Devereux DF, Kent H, Brennan MF. Time dependent effects of adriamycin and X-ray therapy of wound healing in the rat. Cancer. 1980;45:2805–2810.

53. Grillo HC, Potsaid MS. Studies in wound healing: IV. Retardation of contraction by local X-radiation, and observations relating to the origin of fibroblasts in repair. Ann Surg. 1961;154:741–750.

54. Ormsby MV, Hilaris BS, Nori D, et al. Wound complications of adjuvant radiation therapy in patients with soft-tissue sarcomas. Ann Surg. 1989;210(1):93–99.

55. Berkenstock K. Perioperative wound complications following brachytherapy alone or in combination with external beam irradiation in advanced soft-tissue sarcoma of the extremity. Endocuriether/Hyperther Oncol. 1992;8:187–194.

56. Alektiar KM, Zelefsky MJ, Brennan MF. Morbidity of adjuvant brachytherapy in soft tissue sarcoma of the extremity and superficial trunk. Int J Radiat Oncol Biol Phys. 2000;47(5):1273–1279.

57. Lee HY, Cordeiro PG, Mehrara BJ, et al. Reconstruction after soft tissue sarcoma resection in the setting of brachytherapy: a 10-year experience. Ann Plast Surg. 2004;52(5):486–491 discussion 492.

58. Brant TA, Parsons JT, Marcus RB, et al. Preoperative irradiation for soft tissue sarcomas of the trunk and extremities in adults. Int J Radiat Oncol Biol Phys. 1990;19(4):899–906.

59. Stinson SF, DeLaney TF, Greenberg J, et al. Acute and long-term effects on limb function of combined modality limb sparing therapy for extremity soft tissue sarcoma. Int J Radiat Oncol Biol Phys. 1991;21(6):1493–1499.

60. Lin PP, Schupak KD, Boland PJ, et al. Pathologic femoral fracture after periosteal excision and radiation for the treatment of soft tissue sarcoma. Cancer. 1998;82(12):2356–2365.

61. Baldini EH, Goldberg J, Fenner C, et al. Long-term outcomes after function-sparing surgery without radiotherapy for soft tissue sarcoma of the extremities and trunk. J Clin Oncol. 1999;17(10):3252–3259.

62. Rydholm A, Gustafson P, Rooser B, et al. Limb-sparing surgery without radiotherapy based on anatomic location of soft tissue sarcoma. J Clin Oncol. 1991;9(10):1757–1765.

63. Genest P. Iodine-125 as a substitute for iridium-192 in temporary interstitial implants. Endocuriether/Hyperther Oncol. 1985;1:223–228.

64. DiBiase SJ, Rosenstock JG, Shabason L, et al. Tumor bed brachytherapy with a mesh template: an accessible alternative to intraoperative radiotherapy. J Surg Oncol. 1997;66(2):104–109.

65. Chen A, Galloway M, Landreneau R, et al. Intraoperative 125I brachytherapy for high-risk stage I non-small cell lung carcinoma. Int J Radiat Oncol Biol Phys. 1999;44(5):1057–1063.

66. Tepper JE, Suit HD. Radiation therapy alone for sarcoma of soft tissue. Cancer. 1985;56(3):475–479.

67. Jaques DP, Coit DG, Hadju SI, et al. Management of primary and recurrent soft-tissue sarcoma of the retroperitoneum. Ann Surg. 1990;212(1):51–59.

68. Sindelar WF, Kinsella TJ, Chen PW, et al. Intraoperative radiotherapy in retroperitoneal sarcomas. Final results of a prospective, randomized, clinical trial. Arch Surg. 1993;128(4):402–410.

69. Gunderson LL, Willett CG, Harrison LB. Intraoperative radiotherapy, current status. 36th Annual Meeting, American Society for Therapeutic Radiology and Oncology. San Francisco, CA:1994.

70. Zelefsky MJ, Harrison LB, Shiu MH, et al. Combined surgical resection and iridium 192 implantation for locally advanced and recurrent desmoid tumors. Cancer. 1991;67(2):380–384.

71. Wilkins K, Turner R, Dolev JC, et al. Cutaneous malignancy and human immunodeficiency virus disease. J Am Acad Dermatol. 2006;54:189–206.

72. Pearlstone DB, Janjan NA, Feig BW, et al. Re-resection with brachytherapy for locally recurrent soft tissue sarcoma arising in a previously radiated field. Cancer J Sci Am. 1999;5(1):26–33.

73. Nori D, Schupak K, Shiu MH, et al. Role of brachytherapy in recurrent extremity sarcoma in patients treated with prior surgery and irradiation. Int J Radiat Oncol Biol Phys. 1991;20(6):1229–1233.

74. Catton C, Davis A, Bell R, et al. Soft tissue sarcoma of the extremity. Limb salvage after failure of combined conservative therapy. Radiother Oncol. 1996;41(3):209–214.

75. Gieschen HL, Spiro J, Suit HD, et al. Long-term results of intraoperative electron beam radiotherapy for primary and recurrent retroperitoneal soft tissue sarcoma. Int J Radiat Oncol Biol Phys. 2001;50(1):127–131.



If you find an error or have any questions, please email us at admin@doctorlib.info. Thank you!