Control Of Soft Tissue Sarcomas Research Articles

Local relapse of soft tissue sarcoma of the extremities or trunk wall operated on with wide margins without radiation therapy.

The quality of surgical margins is the most important factor affecting local control in soft tissue sarcoma (STS). Despite this, there is no universally accepted consensus on the definition of an adequate surgical margin or on which patients should be offered radiation therapy. This study focuses on local control and its prognostic factors in patients with trunk wall and extremity STS. Adult patients with a final diagnosis of trunk wall or extremity STS referred to a single tertiary referral centre between August 1987 and December 2016 were identified from a prospective institutional database. Patients were treated according to a protocol instituted in 1987. The classification of surgical margins and indications for radiation therapy were based on anatomy and strict definition of surgical margins as metric distance to the resection border. Local treatment was defined as adequate if patients received either surgery with wide margins alone or marginal surgery combined with radiation therapy. Margins were considered wide if the tumour was excised with pathological margins greater than 2.5 cm or with an uninvolved natural anatomical barrier. After treatment, patients were followed up with local imaging and chest X-ray: 5 years for high-grade STS, 10 years for low-grade STS. A total of 812 patients were included with a median follow-up of 5.8 (range 0.5-19.5) years. Forty-four patients had a grade 1 tumour: there were no instances of recurrence in this group thus they were excluded from further analysis. Five-year local control in the 768 patients with grade 2-3 STS was 90.1 per cent in patients receiving adequate local treatment according to the protocol. Altogether, 333 patients (43.4 per cent) were treated with wide surgery alone and their 5-year local control rate was 91.1 per cent. Among patients treated with wide surgery alone, deep location was the only factor adversely associated with local relapse risk in multivariable analysis; 5-year local control was 95.3 per cent in superficial and 88.3 per cent in deep-sited sarcomas (hazards ratio 3.154 (95% c.i. 1.265 to 7.860), P = 0.014). A high local control rate is achievable with surgery alone for a substantial proportion of patients with STS of the extremities or superficial trunk wall.

A Phase 2 Study of 5-Day Preoperative Radiotherapy for Patients With High-Risk Primary Soft Tissue Sarcoma

A Phase 2 Study of 5-Day Preoperative Radiotherapy for Patients With High-Risk Primary Soft Tissue Sarcoma

The role of surgery in soft tissue sarcoma: Can we improve outcome and function towards sporting activities?

SummaryLimb-sparing surgery with pre- or postoperative irradiation has evolved as the standard of care for local tumor control of soft tissue sarcoma while ablative procedures are applied in selected cases only. Adequate excision of sarcoma is prerequisite to guarantee local tumor control. While excision with wide margins has been educated in the past, tumor excision with closer margins has shown to provide similar local tumor control. Beside this oncological aspect, type of surgery and reconstruction impact the functional outcome after sarcoma excision in the extremities, which adds to quality of life for the patients. Satisfactory results have been shown by different scoring systems; however, more recent studies focus on high level activities like sports to define the efficacy of different procedures. This review focuses on recent developments within these two topics.

Optimal post-operative radiation after soft-tissue sarcoma resection is achieved in less than two thirds of cases.

Local control of soft tissue sarcomas frequently involves adjuvant radiation to the surgical resection. When opting for post-operative radiation, care should be taken that radiation is started within some reasonable time after the surgery. We were interested to the proportion of patients who did not recieve optimal post-operative radiation and the variables associated. We retrospectively analyzed a series of 77 patients operated on for an extremity soft-tissue sarcoma and due for post-operative radiotherapy. Patients were considered to have received radiation optimally if radiation was started within 12weeks of surgery. Variables associated with not receiving radiation optimally were looked for using univariable and multivariable regression models. Overall, 26 patients (34%; 95% CI: 23-45%) did not receive radiation optimally. Twenty (26%) did not start radiation within the 12-weeks mark and six (8%) could not have radiation at all. The main reason identified for not receiving radiation on time was the occurrence of a wound complication (14 (54%) patients). An increased body mass index (OR: 1.14; 95% CI: 1.02-1.26; p=0.02) and an older age (OR: 1.55; 95% CI: 1.18-2.14; p=0.04; of note, the OR are for a 10year change) were significantly associated with not receiving radiation optimally. Patients with a social fragility (p=0.04), metastatic spread at presentation (p=0.04), and increased duration of surgery (p=0.02) were more likely to develop a wound complication. About 34% of patients do not receive optimal post-operative radiation treatment. Older and obese patients have a higher risk of not receiving radiation optimally. The decision for pre- or post-operative radiation should account for these findings.

Abstract 2665: NBTXR3 hafnium oxide nanoparticle activated by ionizing radiation demonstrates marked radio-enhancement and antitumor effect via high energy deposit in human soft tissue sarcoma

Abstract Local and systemic control of Soft Tissue Sarcoma (STS) remains a clinical challenge. Radiation therapy is part of the standard of care of STS. The narrowness of its therapeutic window represents the main concern for different clinical settings. Thus, local delivery of radiation doses is critical to ensure optimal benefit-risk ratio. NBTXR3, biocompatible hafnium oxide nanoparticles were designed as therapeutics to be activated by ionizing radiation to achieve tumor control by enhancement of local energy deposition. A global non clinical program was implemented in mesenchymal tumor models. In vitro clonogenic survival assays were performed in two human fibrosarcoma cell lines (HT1080 and Hs913t) and a human liposarcoma cell line (SW872) to evaluate the cellular response to radiation-activated NBTXR3 at increasing concentrations. A marked radio-enhancement was observed in human STS cell lines with dose enhancement factors estimated at 4 Gy ranging from 1.48 up to 5.36 according to NBTXR3 concentrations. Further, in human immortalized MRC5V1 fibroblasts, no significant decrease in clonogenic surviving fraction was observed upon activation of NBTXR3 under similar conditions suggesting a differential radiation response between fibroblasts and fibrosarcoma, liposarcoma cell lines. This differential radiation response was further confirmed between HT1080 fibrosarcoma cell line and MRC5V1 fibroblasts upon activation of NBTXR3 at increasing concentration using high energy gamma-rays. Mechanistic studies have demonstrated in HT1080 cells that NBTXR3 activation induces an increase of 53BP1 foci associated with more “complex” DNA damages than ionizing radiation alone. The level of unrepaired DNA damages was also estimated by flow cytometry analysis showing a higher level of gamma-H2AX at 48h following NBTXR3 activation than after radiotherapy alone. DNA fragmentation and Annexin V staining have demonstrated that these unrepaired DNA damages upon NBTXR3 activation induces apoptosis in HT1080 fibrosarcoma cells. In vivo, tolerance and tumor growth delay were investigated in two human xenografted tumor models, HT1080 fibrosarcoma and a patient derived liposarcoma LPS80T3 (poorly differentiated grade 3). No toxicity related to NBTXR3 was reported. In both models, a significant advantage was demonstrated in terms of tumor growth inhibition and survival when compared to radiation therapy alone. These findings establish a novel approach of treatment, which may be applied to a broad range of tumors. Therefore, incrementing the amount of energy deposited within the tumor through the activation of NBTXR3 crystalline nanoparticles constitutes a revolutionary approach for future clinical investigation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2665. doi:10.1158/1538-7445.AM2011-2665

Femur fractures after limb-sparing treatment of soft-tissue sarcomas: One institution's experience.

e19601 Background: Local control for soft tissue sarcomas of the long bones often includes limb sparing surgery with the addition of radiation therapy. While effective, there are potential complications including poor wound healing and late-onset fractures. Methods: This analysis includes patients treated for a soft tissue sarcoma of the thigh with limb-sparing surgery and radiation therapy between 1986 and 2000 at the University of Minnesota Masonic Cancer Center (n=89). Demographic, tumor, and treatment characteristics including age, sex, histology, location (anterior, posterior, medial, buttock, popliteal fossa), use of adjuvant chemotherapy (yes/no), use of periosteal stripping (yes/no), timing of radiation (pre-/post-operative, both), radiation dose [high (>60 Gy), low (</+60 Gy), radiation field length [> 30 centimeters (cm), </= 30 cm], circumference of radiation field (100%/< 100% of femur) were abstracted from the medical record. Univariate analysis was conducted to identify significant risk factors for fracture. Given the small numbers of patients with a femoral fracture, multivariate analysis was unable to be performed. Results: Survivors (58 % male) with a median age of 50 (7-88) years reported_8 (9%) fractures at a median of 7.3 (0.8 – 21.9) years from diagnosis after a median of 6300 (2000-7020) cGy of radiation. All fractures occurred within the previous radiation field, after minimal or no trauma. Three of the 8 (37.5%) had delayed union, 2 (25%) nonunion healing. Significant risk factors included periosteal stripping (p=0.006), anterior location (p=0.022), and having 100% of the femoral circumference irradiated (p=0.018). Taking into account time to fracture using Kaplan Meier and log rank tests, these same predictors were identified. Older age, female sex, use of chemotherapy, and timing of radiation were not predictive of femoral fracture. Conclusions: Anterior tumor location, the presence of periosteal stripping, and radiation to 100% of the femur circumference are significantly associated with femoral fracture. These patients require long-term monitoring and may warrant prophylactic intramedullary pinning or other protective measures. No significant financial relationships to disclose.

Preoperative Intensity-Modulated Radiotherapy Combined with Temozolomide for Locally Advanced Soft-Tissue Sarcoma

To evaluate the toxicity and efficacy of preoperative intensity-modulated radiotherapy (IMRT) combined with temozolomide to improve local tumor control in soft-tissue sarcoma (STS). A cohort of 15 consecutive patients with nonmetastasized, primary high-grade or locally recurrent Stage III (n = 14) or IIb (n = 1) STS not amenable to surgical resection without significant organ or extremity function loss was prospectively investigated. Median tumor size was 9.8 cm, and most tumors were non-extremity sarcomas. Patients preoperatively received 50 mg/m(2) of temozolomide during IMRT (50.4 Gy). Resection was intended 6 weeks thereafter. Toxicity was assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0, and response was assessed by Response Evaluation Criteria in Solid Tumors. Of 15 patients, 14 completed preoperative treatment. No Grade 4 toxicities occurred. Nausea and vomiting were the most frequent Grade 3 toxicities. The most frequent toxicities of any grade were dermatologic, gastrointestinal, and hematologic. Response was partial response in 5, stable disease in 7, and progressive disease in 2 patients. Ten patients underwent surgery: 7 were resected with clear margins (R0), and 2 patients had an R1 resection; in 1 patient the tumor was not resectable. Postoperative complications occurred in 4 patients. Five patients did not undergo surgery because of intercurrent metastatic disease, unresectable disease, or refusal. Preoperative chemoradiation with temozolomide and IMRT can be administered safely and with promising efficacy in patients with locally advanced STS.

Gemcitabine-Mediated Radiosensitization of Human Soft Tissue Sarcoma

Local and systemic control of soft tissue sarcoma (STS) remains a clinical challenge, particularly for retroperitoneal, deep truncal, or advanced extremity disease. 2',2'-Difluoro-2'-deoxycytidine (gemcitabine) is a potent radiosensitizer in many tumor types, but it has not been studied in human STS. The purpose of this study was to determine the radiosensitizing potential of gemcitabine in preclinical models of human STS. The in vitro radiosensitizing activity of gemcitabine was assessed with clonogenic survival assay on three human STS cell lines: SK-LMS-1 (leiomyosarcoma), SW-872 (liposarcoma), and HT-1080 (fibrosarcoma). Cell cycle distribution was determined using dual-channel flow cytometry. The in vivo radiosensitizing activity of gemcitabine was assessed with subcutaneous SK-LMS-1 nude mice xenografts. Tumor-bearing mice were treated with concurrent weekly gemcitabine and fractionated daily radiotherapy (RT) (2 Gy daily) for 3 weeks (a total dose of 30 Gy). The 50% inhibitory concentration (IC(50)) of gemcitabine for the human STS cell lines ranged from 10 to 1000 nM. Significant in vitro radiosensitization was demonstrated in all three human STS cell lines using gemcitabine concentrations at and below the IC(50). Maximal radiosensitization was associated with accumulation of cells in early S-phase. SK-LMS-1 xenografts displayed significant tumor growth delay with combined gemcitabine and RT compared to either treatment alone. Treatment related toxicity was greatest in the gemcitabine plus RT arm, but remained at an acceptable level. Gemcitabine is a potent radiosensitizer in preclinical models of human STS. Clinical trials combining gemcitabine and RT in human STS are warranted.

Results of treatment of malignant soft tissue tumours in the groin

Soft tissue sarcomas of the inguinal region are a challenge with regard to achieving clear margins, reconstruction of the femoral vessels, and soft tissue coverage. Six men aged 39 to 48 years and one woman of 56 were treated for soft tissue sarcomas of the groin. All patients were treated with local en bloc resections including the femoral artery, vein, and nerve. In two patients the soft tissue defect was covered primarily with an ipsilateral rectus abdominis muscle flap, in two others (because of wound dehiscence) coverage was achieved with the opposite rectus abdominis muscle pedicle flap as we were afraid of closure of the ipsilateral deep epigastric vessels. In the others local measures were sufficient, however, wound healing was usually delayed. Histopathological examination showed tumour-free margins in each case. One patient developed a local recurrence, but had had no radiotherapy because of problems with wound healing. A high rate of local tumour control in soft tissue sarcomas of the inguinal region can be achieved with the combination of surgical resection and radiotherapy. No compromise should be made with aggressive soft tissue coverage to protect the vascular reconstruction, control wound healing after neoadjuvant radiotherapy, or allow immediate adjuvant radiotherapy. At primary wound closure we would generally use an ipsilaterally distally pedicled rectus abdominis muscle flap if the deep epigastric vessels can be preserved or - if the ipsilateral vessels need be resected to achieve clearance of tumour - use a contralateral flap.

Chemotherapy for soft tissue sarcoma

Purpose of review: After reading this article, the reader should understand the evolution of chemotherapy treatment of soft tissue sarcomas, acknowledge the limited efficacy of established chemotherapeutic regimens, and recognize the potential utility of targeted therapies. Recent findings: Relative success in the treatment of gastrointestinal stromal tumors utilizing imatinib mesylate, a selective inhibitor of certain tyrosine kinases, has heralded the development of new oncogene targeted drug therapies. Examples of target proteins include epidermal growth factor receptor/human epidermal growth factor receptor 2, insulin-like growth factor receptor (IGF-1R), fibroblast growth factor receptor1 (FGF1), and vascular endothelium growth factor (VEGF) among others. Summary: Despite excellent regional control of soft tissue sarcoma, a large number of patients (50%) die from metastatic disease. Considering the success of chemotherapy in the treatment of osteosarcoma, systemic chemotherapy for the treatment of soft tissue sarcoma seemed like a natural progression. A review of multiple trials performed since 1997, however, suggests that the efficacy of established chemotherapy regimens is poor. In fact, statistically significant differences at early time points become insignificant at later time points. To date, a critical understanding of the molecular fingerprint of soft tissue sarcoma is missing, knowledge of which will be required both for adequate classification of histologic variants and identification of tumor specific therapy targets.

Impact of the smallest surgical margin on local control in soft tissue sarcoma

The aim was to review a single-institution experience of a prospective treatment protocol for soft tissue sarcoma of the extremity and trunk wall, with particular focus on the smallest surgical margin leading to local control. The study included 270 patients who had surgery for soft tissue sarcoma at Helsinki University Central Hospital between 1987 and 1997. Resection margins were measured prospectively from tumour specimens. Radiotherapy was administered if the smallest margin measured less than 2.5 cm, irrespective of tumour grade. With a median follow-up of 6.6 years, the 5-year local control rate was 76.4 per cent. On multivariable analysis, the smallest surgical margin around the sarcoma (after radiotherapy) was prognostic for local control. A margin of at least 2.5 cm was associated with a local recurrence-free rate of 89.2 per cent at 5 years. Tumour size, depth or grade and patient's age had no independent prognostic effect on local control. Surgical margin had independent prognostic value for local control. A surgical margin of 2-3 cm provided reasonable local control of soft tissue sarcoma, even without radiotherapy. Radiotherapy is recommended for smaller margins, irrespective of tumour grade.

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Local and systemic control of soft tissue sarcoma (STS) remains a clinical challenge, particularly for retroperitoneal or advanced truncal or extremity disease. Gemcitabine is a potent radiosensitizer in many tumor types, but has not been studied in human STS. The purpose of this study was to determine the radiosensitizing potential of gemcitabine in preclinical models of human STS.

Pulsed Dose-Rate Perioperative Interstitial Brachytherapy for Soft Tissue Sarcomas of the Extremities and Skeletal Muscles of the Trunk

This study evaluated the role of pulsed dose-rate (PDR) brachytherapy (BRT), delivered alone or as a boost to external beam radiotherapy, as adjuvant therapy for the local control of soft tissue sarcomas of the extremities and skeletal muscles of the trunk that have undergone surgical treatment. Between July 1998 and January 2002, 42 patients were treated with a combination of surgery and BRT alone (18 patients) or BRT/external beam radiotherapy (24 patients) for the treatment of primary (n = 32) and recurrent (n = 10) soft tissue sarcomas located in the proximal extremity (n = 17), distal extremity (n = 17), and trunk (n = 8). Tumor size was <5 cm in 20 cases and >5 cm in 22 cases, with histological grading of 1 (n = 7), 2 (n = 18), or 3 (n = 17). The median BRT dose delivered was 15 Gy, and the median external beam irradiation dose was 50 Gy. With a median follow-up of 34 months, the 36-month survival was 83.9% (SE, 6.1%), and the local control was 89%. PDR interstitial BRT for soft tissue sarcoma is an effective, well-tolerated adjuvant radiation treatment that offers several practical advantages, among which are low acute and late toxicity with maximum normal tissue and critical structure sparing and overall shorter radiotherapy and hospital stay.

Radiation Therapy for Control of Soft Tissue Sarcomas Resected with Positive Margins

Purpose/Objective: Surgery and radiation therapy (XRT) are employed for treatment of most patients with soft tissue sarcoma (STS). Surgical sparing of normal structures results in positive margins (PM) in some STS patients. Prior studies have documented the adverse impact of a PM in these patients. We have investigated the efficacy of treatment in patients with a positive margin (PM) and evaluated the impact of patient and treatment characteristics on outcome. Materials/Methods: Retrospective chart review was performed on 154 STS patients with PM who were identified in our departmental sarcoma database and who underwent XRT between 1970 and 2001. Tumor location: lower (48%) and upper (20%) extremity, head/neck 15%, retroperitoneal 11%, and trunk 6%. Grade: G1 8%, G2 51%, G3 41%. Local control (LC), disease-free survival (DFS) and overall survival (OS) rates were evaluated by univariate (log-rank) and multivariate analysis with regard to known STS prognostic factors. Results: Median follow-up for living patients is 101 (range: 29–371) months. Surgical procedures were intralesional (32%), marginal (27%), excisional biopsy (22%), and wide excision (19%) Median tumor size was 6 cm (range 1.5–33 cm). Depth was 88% deep and 12% superficial. Median XRT dose was 64 Gy (range: 20–77 Gy). Chemotherapy was given to 15% of patients. At 2 and 5 years, actuarial LC, DFS, and OS rates were: 84.9% and 76%, 65.6% and 46.7 %, and 81.1% and 65.2% respectively. Patients with grossly PM tended to fare worse, with LC and OS at 5 years of 67% and 52.2% versus 81% and 73.4% with microscopic PM, p=0.09. LC was better in superficial lesions, 93.3% vs. 66%, p=0.05. LC was highest in patients with extremity lesions. Patients receiving >64 Gy had 5-year LC, DFS and OS rates of 85%, 52.1% and 67.8% versus 66.1%, 41.8% and 62.9% if <≤ 64 Gy, p<0.04. LC was significantly higher in patients receiving doses >64 Gy (see figure). OS in patients with G2/G3 tumors at 5 years was 67.3% in patients with LC versus 49.2% if local failure (LF) occurred, p< 0.001. Other known prognostic factors including grade, stage, size, and age (>≥ 50) also significantly influenced OS. By multivariate analysis, the best predictors of LC were site (extremity vs. other) p<0.01 and dose (> 64 vs. ≤ 64 Gy) p<0.05; the best predictor of DM was size (≤ 5 cm vs. > 5 cm), p<0.05; and the best predictors for OS were size p<0.001, gross versus microscopic PM p<0.05, and LF p<0.01. Conclusions: Radiation therapy secures LC in most STS patients resected with positive margins. Doses > 64 Gy, superficial location, and extremity site are associated with improved local control. Overall survival is worse in patients with lesions > 5 cm, grossly PM, and LF.

Interval between surgery and radiotherapy: effect on local control of soft tissue sarcoma*1

Interval between surgery and radiotherapy: effect on local control of soft tissue sarcoma*1

Interval between surgery and radiotherapy: effect on local control of soft tissue sarcoma

Purpose To evaluate the clinical significance of the interval between surgery and postoperative radiotherapy (RT) for patients with soft tissue sarcoma. Methods and materials The records of 799 patients who underwent postoperative RT for soft tissue sarcoma between 1960 and 2000 were retrospectively reviewed. Univariate and multivariate analyses were used to evaluate the potential impact of the timing of postoperative RT on the rate of local control (LC). Results The actuarial overall LC rate was 79% at 10 years and 78% at 15 years. Univariate analysis indicated that the factors associated with an inferior 10-year LC rate were positive resection margins ( p <0.0001); treatment for recurrent disease ( p <0.0001); primary location in the head and neck or deep trunk ( p <0.0001); age >64 years ( p <0.0001); histopathologic subtype of malignant fibrous histiocytoma, neurogenic sarcoma, or epithelioid sarcoma ( p = 0.01); tumor size >10 cm ( p = 0.02); postoperative radiation dose <64 Gy ( p = 0.03); and high histologic grade ( p = 0.05). On multivariate analysis, all these factors remained statistically significant, except for high histologic grade and large size. A delay between surgery and the start of RT of >30 days was associated with a decreased 10-year LC rate, but this association was not statistically significant (76% vs. 83%, p = 0.07). The potential association between RT delay and inferior LC could be explained by an imbalance in the distribution of other prognostic factors. Conclusion The interval between surgery and RT did not significantly impact the 10-year LC rate. These findings indicate that an RT delay should not be viewed as an independent adverse factor for LC and that treatment intensification may not be necessary for patients in whom a treatment delay has already occurred.

The effect of delayed postoperative irradiation on local control of soft tissue sarcomas of the extremity and torso

Purpose : The impact of delayed adjuvant radiotherapy in patients treated by surgical resection for peripheral or torso soft tissue sarcoma has not been well characterized. We retrospectively examined this issue in an institutional patient cohort. Methods and Materials : One hundred two adult patients were treated at the University of Washington Medical Center between 1981 and 1998 with postoperative radiotherapy for cure of a newly diagnosed soft tissue sarcoma. Of this group, 58 patients had primary intermediate- or high-grade disease of the extremity or torso (50 extremity/8 torso). Tumor histology was predominantly malignant fibrohistiocytoma, synovial cell sarcoma, and leiomyosarcoma. The group was dichotomized according to time interval from definitive resection to the start of adjuvant radiation. Twenty-six patients had a short delay, defined as <4 months, and 32 patients had a long delay of ≥4 months. Both groups were balanced with regard to site, size, margin status, and tumor depth; however, the long-delay group had a larger proportion of high histologic grade lesions and was treated more frequently with chemotherapy (31/32 [97%] for long-delay patients vs. 14/26 [54%] for short-delay patients). Median follow-up was 49.5 months (range: 7–113 months). Median follow-up for patients still alive was 54 months (range: 9–113 months). Survival outcomes were estimated by the Kaplan-Meier method. Results : Overall local relapse-free survival at 5 years from the time of definitive resection was 74%. On univariate analysis, estimated 5-year local relapse-free survival was significantly improved in the short-delay group (88% vs. 62% for the long-delay group, p = 0.048 by log rank). Overall distant relapse-free survival, disease-free survival, and overall survival at 5 years were 77%, 68%, and 86%, respectively. These survival outcomes were statistically equivalent in both radiation delay groups. There was no evidence to suggest that delaying adjuvant systemic therapy for postoperative radiation negatively impacted distant relapse-free survival, disease-free survival, or overall survival. Patterns of failure analysis revealed that 11/12 disease failures in the long-delay group had a local component, with five patients presenting with solitary local recurrences. Severe chronic radiation-related soft tissue or peripheral nerve morbidity was infrequent (5/58 or 8.6%) and similar in both groups. Conclusions : Postoperative radiation delays of 4 months or greater were associated with inferior local disease control for intermediate- and high-grade soft tissue sarcomas of the extremity and torso. Our results suggest that timing postoperative radiation before postoperative chemotherapy may optimize local therapy for such patients without adversely affecting distant disease control, long-term morbidity, or overall survival. Prospective testing of this hypothesis is warranted.

More is Less: Systemic Treatment for Local Control in Soft Tissue Sarcoma

More is Less: Systemic Treatment for Local Control in Soft Tissue Sarcoma

Morbidity of adjuvant brachytherapy in soft tissue sarcoma of the extremity and superficial trunk

Purpose: We have previously shown that adjuvant brachytherapy (BRT) improves local control in soft tissue sarcoma (STS) of the extremity and superficial trunk. A detailed assessment of the morbidity of this approach has not been examined. The purpose of this study was to evaluate the toxicity associated with adjuvant BRT in terms of wound complications, bone fracture, and peripheral nerve damage. Methods and Materials: Between July 1982 and June 1992, 164 adult patients with STS of the extremity or superficial trunk were randomized intraoperatively to receive or not to receive BRT after complete resection. BRT was delivered with 192Ir to a total dose of 42–45 Gy. The BRT and no-BRT arms were balanced with regard to age, sex, presentation (primary vs. recurrent), site, grade, size, and depth. Morbidity was assessed in terms of significant wound complication, bone fracture, and peripheral nerve damage (grade ≥ 3). The significant wound complications were defined as those wound problems requiring operative revision for coverage or threatened limb loss, persistent seroma requiring repeated aspirations and/or drainage, wound separation > 2 cm, hematoma > 25 ml, and/or purulent wound discharge. The median follow-up was 100 months. Results: The significant wound complication rate was 24% in the BRT group and 14% in the no-BRT group, ( p = 0.13). The rate of wound reoperation, however, was significantly higher in the BRT arm (10% vs. 0%; p = 0.006). Examination of other covariables that may have contributed to wound reoperation revealed the width of the excised skin (WES) to be a significant factor [1% (WES ≤ 4 cm) vs. 10% (WES > 4 cm), p = 0.02]. Bone fracture only occurred in patients receiving BRT (n = 3, 4%), although this was not statistically significant ( p = 0.2). The rate of peripheral nerve damage, however, was similar in both arms (7% vs. 7%). Conclusion: The overall morbidity associated with adjuvant BRT was not significantly higher than that with surgery alone. However, BRT and WES > 4 cm were associated with significantly higher wound reoperation rate. This has significant implications for strategies designed to maximize wound coverage in patients who receive BRT.

Chapter 4: Surgery for local control of soft tissue sarcoma

Chapter 4: Surgery for local control of soft tissue sarcoma