Radiotherapy For Soft Tissue Sarcoma Research Articles

Radiotherapy for Soft Tissue Sarcoma of the Proximal Lower Extremity

Soft-tissue sarcoma (STS) is a histopathologically diverse group of tumors accounting for approximately 10,000 new malignancies in the US each year. The proximal lower extremity is the most common site for STS, accounting for approximately one-third of all cases. Coordinated multimodality management in the form of surgery and radiation is often critical to local control, limb preservation, and functional outcome. Based on a review of currently available Medline literature and professional experience, this paper provides an overview of the treatment of STS of the lower extremity with a particular focus on the modern role of radiotherapy.

Outcomes following Resection and Radiotherapy for Soft Tissue Sarcomas of the Extremity and Superficial Trunk: The University of Michigan Experience

Outcomes following Resection and Radiotherapy for Soft Tissue Sarcomas of the Extremity and Superficial Trunk: The University of Michigan Experience

Setup Uncertainty Analysis for Intensity-modulated Radiotherapy for Soft Tissue Sarcoma of the Thigh

Use of the proper setup uncertainty margins in radiation therapy planning is important to ensure that the clinical target volume (CTV) is covered while preserving as much normal tissue as possible. Setup uncertainty has been extensively studied in the head and neck and pelvic regions, however, data is only now starting to emerge for extremity irradiation. Treatment of the thigh represents unique challenges in positioning and immobilization due to its ability to undergo many translations and rotations relative to the rest of the body. We evaluate three dimensional (3D) setup errors and report CTV to planning target volume (PTV) margins for soft tissue sarcoma patients undergoing intensity modulated radiation therapy (IMRT) to the thigh. Twenty-one patients immobilized in an Alpha cradle mold and treated via IMRT to the thigh between 2006 and 2008, a total of 114 pairs of orthogonal megavoltage portal images, were analyzed retrospectively using a template based matching technique. Individual setup errors, maximum and minimum displacements, and population based systematic (Σ) and random (σ) errors were calculated. Setup margins were then determined using published margin recipes. The mean translational setup errors (and range max to min) from all data were 1 (+21 to -15), 0 (+19 to -10), and 1 (+8 to -6) millimeters (mm) in the right-left (RL), anterior-posterior (AP), and superior-inferior (SI) directions respectively. The mean rotational errors from all data were -0.1° (+3.5° to -9°) and 0.2° (+6.5° to -4.5°) in the cranial and sagittal planes respectively. In the RL, AP, and SI directions, the standard deviation of the patient systematic errors was 4, 3, and 2 mm and the root mean square of the patient random errors was 4, 4, and 2 mm. This corresponds to a CTV to PTV margin of 12.5 (RL), 10.7 (AP), and 6.1 (SI) mm using the van Herk margin recipe formulation. Our institutional experience in IMRT for soft tissue sarcoma of the thigh provides useful data for the quantification of setup errors for this anatomical site. The observed population systematic and random errors for the thigh are comparable to reports in the literature for pelvic sites with similar immobilization methods. A CTV to PTV expansion of ≤ 12.5 mm should result in adequate CTV coverage for this patient population.

Inhibition of mTOR Radiosensitizes Soft Tissue Sarcoma and Tumor Vasculature

The PI3K/Akt/mTOR prosurvival pathway is frequently up-regulated in soft tissue sarcoma. Mammalian target of rapamycin (mTOR) inhibitors, such as rapamycin, have recently shown clinical benefit in soft tissue sarcoma, and mTOR inhibition has also been associated with radiosensitization of carcinoma and endothelial cells. This study tested the hypothesis that rapamycin radiosensitizes soft tissue sarcoma and endothelial cells in vitro and in vivo through the inhibition of mTOR. Colony formation assays were done to determine the radiosensitizing properties of rapamycin on three human soft tissue sarcoma cell lines (SK-LMS-1, SW-872, and HT-1080) and human dermal microvascular endothelial cells (HDMEC). The functional effects of rapamycin and radiation on the endothelial compartment were evaluated with microvascular sprouting assays. The in vivo radiosensitizing activity of rapamycin was assessed with s.c. SK-LMS-1 nude mice xenografts treated with concurrent daily rapamycin, radiation, or both for three weeks. In vitro radiosensitization was shown in all three soft tissue sarcoma cell lines with minimally cytotoxic doses of rapamycin. SK-LMS-1 xenografts displayed significant tumor growth delay with rapamycin and radiation compared with either treatment alone. Radiation resulted in transient increased mTOR function, whereas rapamycin abolished this signaling in irradiated and unirradiated samples. In HDMEC, rapamycin and radiation reduced microvessel sprouting, but did not alter colony formation. Minimally cytotoxic concentrations of rapamycin inhibited the mTOR cascade in culture and in vivo while radiosensitizing soft tissue sarcoma, and produced synergistic effects with radiation on HDMEC microvessel formation. By targeting both tumor and endothelial compartments, rapamycin produced potent radiosensitization of soft tissue sarcoma xenografts. Clinical trials combining rapamycin and radiotherapy in soft tissue sarcoma are warranted.

A Device and Procedure for Immobilization of Patients Receiving Limb-Preserving Radiotherapy for Soft Tissue Sarcoma

The purpose of this study was to determine the accuracy and efficiency of a custom-designed immobilization device for patients with extremity soft-tissue sarcoma. The custom device consisted of a thermoplastic shell, vacuum pillow, and adaptable baseplate. The study included patients treated from January 2005 to March 2007, with 92 patients immobilized with the custom device and 98 with an established standard. Setup times for these cohorts were analyzed retrospectively for conformal and intensity modulated radiotherapy techniques (IMRT). Thigh tumor setup times were analyzed independently. A subset of patients treated with IMRT was analyzed for setup error using the radiographically verified isocenter position measured daily with electronic portal imaging and cone-beam computed tomography. Mean setup time was reduced by 2.2 minutes when using the custom device for conformal treatment ( p = 0.03) and by 5.8 min for IMRT of thigh tumors ( p = 0.009). All other setup time comparisons were not significant. A significant systematic error reduction was seen in all directions using the custom device. Random error standard deviations favored the custom device. The custom device offers immobilization advantages. Patient setup time was reduced for conformal techniques and IMRT of thigh tumors. Positioning uncertainty was improved, permitting a reduction of the planning target volume margin by 2 to 4 mm.

Evaluation of Radiological and Pathological Response Following Pre-operative Radiotherapy of Soft-tissue Sarcoma

Evaluation of Radiological and Pathological Response Following Pre-operative Radiotherapy of Soft-tissue Sarcoma

Isolated Limb Perfusion and External Beam Radiotherapy for Soft Tissue Sarcomas of the Extremity: Long-Term Effects on Normal Tissue According to the LENT-SOMA Scoring System

BackgroundWith the combined treatment procedure of isolated limb perfusion (ILP), delayed surgical resection and external beam radiotherapy (EBRT) for locally advanced soft tissue sarcomas (STS) of the extremities, limb salvage rates of more than 80% can be achieved. However, long-term damage to the healthy surrounding tissue cannot be prevented. We studied the late effects on the normal tissue using the LENT-SOMA scoring system.Patients and MethodsA total of 32 patients—median age 47 (range 14–71) years—were treated for a locally advanced STS with ILP, surgical resection and often adjuvant 60–70 Gy EBRT. After a median follow-up of 88 (range 17–159) months, the patients were scored, using the LENT-SOMA scales, for the following late tissue damage: muscle/soft tissue, peripheral nerves, skin/subcutaneous tissue and vessels.ResultsAccording to the individual SOM parameters of the LENT-SOMA scales, 20 patients (63%) scored grade-3 toxicity on one or more separate items, reflecting severe symptoms with a negative impact on daily activities. Of these patients, 3 (9%) even scored grade-4 toxicity on some of the parameters, denoting irreversible functional damage necessitating major therapeutic intervention.ConclusionsIn evaluating long-term morbidity after a combined treatment procedure for STS of the extremity, using modified LENT-SOMA scores, two-thirds of patients were found to have experienced serious late toxic effects.

Preoperative radiotherapy for soft tissue sarcoma: The Peter MacCallum Cancer Centre experience

Preoperative radiotherapy for soft tissue sarcoma: The Peter MacCallum Cancer Centre experience

Target Volume Delineation for Postoperative Radiotherapy of Soft Tissue Sarcoma: Impact of Digital Fusion of Preoperative Images With Postoperative Images

Target Volume Delineation for Postoperative Radiotherapy of Soft Tissue Sarcoma: Impact of Digital Fusion of Preoperative Images With Postoperative Images

Long-Term Locoregional Vascular Morbidity After Isolated Limb Perfusion and External-Beam Radiotherapy for Soft Tissue Sarcoma of the Extremity

BackgroundIsolated limb perfusion (ILP) with tumor necrosis factor alpha (TNF-α) and melphalan, followed by delayed surgical resection and adjuvant external-beam radiotherapy is a limb salvage treatment strategy for locally advanced soft tissue sarcomas. The long-term vascular side effects of this combined procedure were evaluated.MethodsThirty-two patients were treated for a locally advanced sarcoma of the upper (n = 5) or lower limb (n = 27). All patients underwent a noninvasive vascular work-up.ResultsFive patients underwent a leg amputation, in two cases due to critical leg ischemia 10 years after ILP. With a median follow-up of 88 (range, 17–159) months, none of the patients with a salvaged lower leg (n = 22) experienced peripheral arterial occlusive disease. Ankle-brachial index (ABI) measurements in the involved leg (median, 1.02; range, .50–1.20) showed a significant decrease compared with the contralateral leg (median, 1.09; range, .91–1.36, P = .001). Pulsatility index (PI) was decreased in the treated leg in 17 of 22 patients at the femoral level (median, 6.30; range, 2.1–23.9 vs. median, 7.35; range, 4.8–21.9; P = .011) and in 19 of 20 patients at popliteal level (median, 8.35; range, 0–21.4 vs. median, 10.95; range, 8.0–32.6; P < .0005). In patients with follow-up of >5 years, there was more often a decrease in ABI (P = .024) and PI at femoral level (P = .011).ConclusionsILP followed by resection and external-beam radiotherapy can lead to major late vascular morbidity that requires amputation. Objective measurements show a time-related decrease of ABI and femoral PI in the treated extremity.

Radiation planning comparison for superficial tissue avoidance in radiotherapy for soft tissue sarcoma of the lower extremity

Three types of preoperative radiotherapy (RT) plans for extremity soft tissue sarcoma were compared to determine the amount of dose reduction possible to the planned surgical skin flaps required for tumor resection and wound closure, without compromising target coverage. Twenty-four untreated patients with large, deep, lower extremity STS treated with preoperative RT and limb salvage surgery had their original conventional treatment plans re-created. The same clinical target volume was used for all three plans. The future surgical skin flaps were created virtually through contouring by the treating surgeon and regarded as an organ at risk. The original, conformal, and intensity-modulated RT (IMRT) plans were created to deliver 50 Gy in 25 fractions to the clinical target volume. Clinical target volume and organ-at-risk dose-volume histograms were calculated and the plans compared for conformality, target coverage, and dose sparing. The mean dose to the planned skin flaps was 42.62 Gy (range, 30.24-48.65 Gy) for the original plans compared with 40.12 Gy (range, 24.24-47.26 Gy) for the conformal plans and 26.71 Gy (range, 22.31-31.91 Gy) for the IMRT plans (p = 0.0008). An average of 86.4% (range, 53.2-97.4%) of the planned skin flaps received >or=30 Gy in the original plans compared with 83.4% (range, 36.2-96.2%) in the conformal plans and only 34.0% (range, 22.5-53.3%) in the IMRT plans (p = 0.0001). IMRT improved target conformality compared with the original and conformal plans (1.27, 2.34, and 1.76, respectively, p = 0.0001). In a retrospective review, preoperative IMRT substantially lowered the dose to the future surgical skin flaps, sparing a greater percentage of this structure's volume without compromising target (tumor) coverage.

Preoperative radiotherapy for soft tissue sarcoma: The Peter MacCallum Cancer Centre experience

Aim Radiotherapy has been shown to improve local control in combination with limb-sparing or conservative surgery in the management of localised soft tissue sarcoma. Our centre's treatment protocol is to offer preoperative external beam radiotherapy (50.4 Gy in 28 fractions) followed by surgery four to six weeks later. The aim of this study is to review the treatment outcome and toxicity of patients treated with this protocol. Methods Consecutive patients with localised extremity or truncal soft tissue sarcoma who presented between January 1996 and December 2000 and treated with preoperative radiotherapy followed by limb-sparing surgery were reviewed. Patients with recurrent disease or metastatic disease at diagnosis and patients below the age of 16 years were excluded. Local and distant recurrence, overall survival and treatment toxicity were analyzed. Results Sixty-seven cases were identified (41 males and 26 females). The median age was 52 years (range 17 to 82). The majority (79%) had tumours located in the lower limb. The most common histological diagnoses were malignant fibrous histiocytoma and liposarcoma. The median follow-up was 4.1 years (range 0.6 to 6.9). There were six local recurrences, two of which were successfully salvaged. Twenty patients developed distant metastases. The estimated 5-year actuarial local recurrence free, distant recurrence free and overall survival were 93%, 68% and 73% respectively. Acute radiotherapy toxicity and wound complications were acceptable and late toxicity was uncommon. Conclusion Preoperative radiotherapy followed by surgery provides effective local control in the management of soft tissue sarcoma.

Perioperative Hyperfractionated High-Dose Rate Brachytherapy Combined with External Beam Radiotherapy in the Treatment of Soft Tissue Sarcomas

Low-dose rate brachytherapy alone or in combination with external beam radiotherapy represents a well-established adjuvant treatment in soft tissue sarcomas following surgical resection. The experience with high-dose radiotherapy in this indication is limited. The purpose of our study was an evaluation of the viability of perioperative hyperfractionated high-dose rate brachytherapy in combination with external beam radiotherapy for primary and recurrent soft tissue sarcomas. From February 1998 through June 2002, 10 adult patients with soft tissue sarcomas were treated by interstitial perioperative high-dose rate brachytherapy and external beam radiotherapy. TNM classification was pT2bpN0pM0 in 9 patients and pT1bpN0pM0 in 1 patient. Grade of differentiation was G1 (2 patients), G2 (n = 1), G3 (n = 5), G4 (n = 2). Surgical margins were negative in 7 cases, close in 2 cases and positive in 1 case. The tumor was localized in an extremity in all cases. Hyperfractionation 3 Gy twice daily at 10 mm from the plane of sources was used for brachytherapy, with total doses 18-30 Gy. The patients received external beam radiotherapy with doses 40-50 Gy after brachytherapy. Follow-up periods were between 24-71 months (median, 46). Local control of the disease was achieved in all 10 patients. Distant metastases occurred in 2 cases. One patient was disease free after salvage surgery and chemotherapy, and one patient died of lung disease progression 14 months after brachytherapy. In one case, subcutaneous fistula occurred after radiotherapy and was cured by an excision. Six patients experienced grade 1 or 2 fibrosis and 1 case a mild peripheral neuropathy was recorded. Our study on a small number of patients suggests that perioperative hyperfractionated high-dose rate brachytherapy with doses 8 x 3 Gy in combination with external beam radiotherapy 40-50 Gy is a promising method to achieve high biological doses in the postoperative radiotherapy of soft tissue sarcomas without severe late morbidity and warrants further research.

Results of radiation therapy for unresected soft-tissue sarcomas

Definitive radiotherapy is uncommonly used in the management of soft-tissue sarcoma (STS). The purpose of the study was to evaluate the results of radiotherapy for unresected STSs treated in a single institution. Between 1970 and 2001, 112 patients with STSs underwent radiotherapy for gross disease. Locations of the tumor were 43% in the extremities, 26% retroperitoneal, 24% in the head and neck, and 7% in the truncal wall. Histologic grades were 11% G1 and 89% G2 to G3. Median size of tumor at radiotherapy was 8 cm (range, 1-30 cm). Median radiation dose was 64 Gy (range, 25-87.5 Gy). Twenty percent of patients received chemotherapy. Local control (LC), disease-free survival (DFS), and overall survival (OS) rates were evaluated in univariate (log-rank) and then multivariate (Cox model) analysis to determine prognostic factors for STS. Median follow-up for patients is 139 months (range, 30-365 months). The 5-year actuarial LC, DFS, and OS were 45%, 24%, and 35%, respectively. Tumor size at radiotherapy and radiation dose influenced LC, DFS, and OS in univariate analysis. LC at 5 years was 51%, 45%, and 9% for tumors less than 5 cm, 5 to 10 cm, and greater than 10 cm, respectively. Patients who received doses of less than 63 Gy had 5-year LC, DFS, and OS rates of 22%, 10%, and 14%, respectively, compared with 5-year LC, DFS, and OS rates of 60%, 36%, and 52%, respectively, for patients who received doses of 63 Gy or more. AJCC stage was related to the OS and DFS without statistically significant influence on LC. Use of chemotherapy, histologic grade, age, and location did not influence results. In multivariate analysis, LC was related to total dose (p = 0.02), T size at radiotherapy (p = 0.003), and AJCC stage (p = 0.04); DFS was related to total dose (p = 0.007), T size at radiotherapy (p = 0.01), and AJCC stage (p < 0.0001); and OS was related to AJCC stage (p = 0.0001) and total dose (p = 0.002), but not to T size, at radiotherapy. Major radiotherapy complications were noted in 14% of patients; 27% of patients who received doses of 68 Gy or more had these complications compared with 8% of patients treated with doses of less than 68 Gy. Definitive radiotherapy for STS should be considered in clinical situations where no acceptable surgical option is available. Higher radiation doses yield superior tumor control and survival. A rise in complications occurs in patients who receive doses of 68 Gy or more, which provides a therapeutic window for benefit in these patients.

Influence of site on the therapeutic ratio of adjuvant radiotherapy in soft-tissue sarcoma of the extremity

The ultimate goal of adjuvant radiotherapy (RT) in soft-tissue sarcoma of the extremity is to improve the therapeutic ratio by increasing local control while minimizing morbidity. Most efforts in trying to improve this ratio have focused on the sequencing of RT and surgery, with little attention to the potential influence of the tumor site. The purpose of this study was to determine the influence of tumor site on local control and complications in a group of patients with primary high-grade soft-tissue sarcoma of the extremity treated at a single institution with postoperative RT. Between July 1982 and December 2000, 369 adult patients with primary high-grade soft-tissue sarcoma of the extremity were treated with limb-sparing surgery and postoperative RT. Patients who underwent surgery or RT outside our institution were excluded. The tumor site was the upper extremity (UE) in 103 (28%) and the lower extremity (LE) in 266 (72%). The tumor was < or = 5 cm in 98 patients (27%), and the microscopic margins were positive in 44 (12%). Of the 369 patients, 104 (28%) underwent postoperative external beam RT (EBRT), 233 (63%) postoperative brachytherapy (BRT), and 32 underwent a combination (9%); 325 (88%) received a "conventional" radiation dose, defined as 60-70 Gy for EBRT, 45 Gy for BRT, and 45-50 Gy plus 15-20 Gy for EBRT plus BRT. Complications were assessed in terms of wound complications requiring repeat surgery, fracture, joint stiffness, edema, and Grade 3 or worse peripheral nerve damage. The UE and LE groups were balanced with regard to age, depth, margin status, and type of RT (EBRT vs. BRT +/- EBRT). However, more patients in the UE group had tumors < or = 5 cm and more received a conventional radiation dose (p = 0.01 and P = 0.03, respectively). With a median follow-up of 50 months, the 5-year actuarial rate of local control, distant relapse-free survival, and overall survival for the whole population was 82% (95% confidence interval [CI], 77-86%), 61% (95% CI, 56-66%), and 71% (95% CI, 66-76%), respectively. The 5-year local control rate in patients with UE STS was 70% (95% CI, 60-80%) compared with 86% (95% CI, 81-91%) for LE STS (p = 0.0004). On multivariate analysis, an UE site (p = 0.001; relative risk [RR], 3; 95% CI, 2-5) and positive resection margins (p = 0.02; RR, 2; 95% CI, 1-4) were significant predictors of poor local control. The RT type or radiation dose, age, tumor depth, and size were not significant predictors of local control. The 5-year wound reoperation rate was 1% (95% CI, 0-3) in the UE compared with 11% (95% CI, 7-15) in the LE (p = 0.002). On multivariate analysis, the UE site retained its significance as a predictor of low wound complications (p = 0.001; RR, 0.08; 95% CI, 0.01-0.7). The site did not significantly influence the incidence of fracture (p = 0.7), joint stiffness (p = 0.2), edema (p = 0.5), or Grade 3 or worse peripheral nerve damage (p = 0.3). The UE site is associated with a greater rate of local recurrence compared with the LE. This difference was independent of other variables and could not be accounted for by an imbalance between the two groups. With a lower wound complication rate associated with an UE site, it would be of interest to determine whether preoperative RT and/or intensity-modulated RT can increase the local control in UE sarcomas, thus improving the therapeutic ratio.

Intensity-modulated radiotherapy for soft tissue sarcoma of the thigh

purpose Fracture of the femur is one of the late complications of adjuvant radiotherapy for patients with soft tissue sarcomas of the thigh, who receive external beam irradiation after limb-sparing surgery. When the target volume approximates the femur, it is often inevitable that a large segment of the femur will receive full prescription dose with conventional radiation techniques. We report the dosimetric feasibility of intensity- modulated radiation therapy (IMRT) techniques to achieve adequate target coverage and bone sparing. Methods and materials Treatment planning was performed using both three-dimensional conformal radiotherapy (3D-CRT) and IMRT techniques for 10 patients with soft tissue sarcoma of the thigh with tumor approaching the femur. None of the patients had bony involvement. For all patients, the gross total volume (GTV) and the femur were contoured. The clinical target volume (CTV) was defined as the GTV with a 1.5-cm margin axially, except at the bone interface where the bone interface was used as CTV if the 1.5-cm axial margin extended beyond the bone interface. In the superior-inferior direction, the CTV margin placed around the GTV varied from 5 to 10 cm. The planning target volume (PTV) was defined as the CTV with 5-mm margin all around. The 3D conformal technique consisted primarily of two to three beams with wedges or partial transmission blocks as compensators. For the IMRT technique, five coplanar beams were used, chosen so as to spare much of the surrounding soft tissue and to clear the other extremity or groin areas. IMRT plans were designed to adequately treat the planning target volume and spare the femur as much as possible. Results Dose distributions and dose–volume histograms were analyzed. PTV coverage was comparable with both IMRT and 3D-CRT plans. Dose distributions were more conformal with IMRT, however, especially for patients with large variations of contours. The volume of the femur receiving at least full prescription (63 Gy) V100 decreased on average by approximately 57%, from 44.7 ± 16.8% with 3D-CRT to 18.6 ± 9.2% with IMRT ( p < 0.01). For 3 patients with a GTV surrounding <50% of the circumference of the femur, the reduction in the V100 to the femur ranged from 61% to 79%. The hot spots in the femur, as measured by D05 (the dose encompassing 5% of volume), reduced on average from 67.2 ± 1.8 Gy with 3D-CRT to 65.0 ± 1.2 Gy with IMRT ( p < 0.01). The mean dose to the femur was on average 38.5 ± 11.5 Gy with IMRT, compared with 40.9 ± 12.7 Gy with 3D-CRT. The volume of the surrounding soft tissues, defined as the ipsilateral limb excluding the PTV and the femur, receiving at least prescription dose (63 Gy) was reduced on average by about 78%, from 997 ± 660 cc with 3D-CRT to 201 ± 144 cc with IMRT ( p < 0.01). The D05 to the surrounding soft tissues was on average 58.7 ± 4.7 Gy with IMRT, compared to 67.8 ± 1.3 Gy with 3D-CRT ( p < 0.01), a reduction of approximately 13%. The mean dose to the surrounding soft tissues was comparable in both plans. The volume of the skin (from surface to 5 mm depth) receiving prescription dose (63 Gy) declined by roughly 45%, from 115 ± 40 cc with 3D-CRT to 61 ± 20 cc with IMRT ( p < 0.01), with IMRT providing full skin dose coverage to scars. The hot spots in the skin decreased from 68.0 ± 1.7 Gy with 3D-CRT to 65.2 ± 1.2 Gy with IMRT ( p < 0.01). The mean dose to the skin lessened from 51.5 ± 4.7 Gy with 3D- CRT to 44.0 ± 4.2 Gy with IMRT ( p < 0.01), a reduction of 14%. Conclusions Intensity-modulated radiation therapy techniques can reduce the dose to the femur without compromising target coverage by achieving concave dose distributions around the interface of the PTV and the femur. At the same time, IMRT can reduce the hot spots significantly in the surrounding soft tissues and skin. Whether such dosimetric improvements can translate into reduction of complications and/or improving local control needs to be investigated.

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.

831 Post-operative radiotherapy for soft tissue sarcoma of the anterior compartment of the thigh: should the sartorius muscle be included?

Since 1980 the pyriform scale, Protopulvinaria pyriformis (Cockerell) (Homoptera: Coccidae), has been an important pest of avocado in Israel.Field evaluation showed differences in the susceptibility of avocado cultivars to P. pyriforms; Nabal were the most infested, followed by Hass and Fuerte, whereas Ettinger was sometimes attacked when located close to infested Nabal or Hass trees.In a laboratory experiment P. pyriformis was able to develop and to reproduce on Nabal, Ein Vered and, to a lesser extent, on Hass. Survival of P. pyriformis populations was very low on Fuerte, Horshim and Wurz cultivars, whereas P. pyriformis settled more successfully on Ettinger, Pinkerton and Reed. Results from the laboratory experiment confirmed the actual infestation rates in avocado orchards.

Recent advances in radiotherapy for soft-tissue sarcoma.

The use of radiotherapy in soft-tissue sarcoma continues to evolve. This review focuses on how current management is influenced by the most recent publications in the field. In particular, experience of patients treated without radiotherapy permits guidelines to be established that define a subset of patients who do not need radiotherapy to achieve sarcoma cure with good function. Strategies for radiotherapy delivery are discussed, including the most recent prospective results from a trial of preoperative and postoperative radiotherapy, with particular emphasis on randomized data. Also, the definitions for adequacy of surgical excision and the ability to achieve high rates of local control when margins are minimally positive are integrated into a planned approach. The difficult problem of retroperitoneal sarcoma is discussed, as are chemoradiotherapy protocols that may enhance local and systemic outcome. Finally, the potential for image-guided radiotherapy, enhanced targeting, and better radiotherapy delivery in the contemporary era is addressed.

Significance of dose in postoperative radiotherapy for soft tissue sarcoma

Purpose For soft tissue sarcoma, adjuvant postoperative radiotherapy improves the local control rate over surgery alone. However, the issue of a dose–control relationship is controversial and was addressed in this study. Methods and materials We retrospectively reviewed the records of 775 consecutive patients who received postoperative external beam radiotherapy and used univariate and multivariate analysis to determine whether a dose–control relationship exists for the whole group and for specific high-risk subgroups. Results With a median follow-up of 12.3 years, overall local control rates were 82%, 80%, and 79% at 5, 10, and 15 years. Factors adverse for local control were positive resection margins; tumor location in the head and neck and deep trunk; presentation with locally recurrent disease; patient age >64 years; histopathologic subtype of malignant fibrous histiocytoma, neurogenic sarcoma or epithelioid sarcoma; and tumor size >10 cm. In multivariate analysis, radiation dose ≥64 Gy vs. <64 Gy independently correlated with improved local control. Significant interactions were noted between increased effectiveness of a higher dose and presentation with locally recurrent disease, with head and neck and deep trunk tumor sites, and with positive or uncertain resection margins such that local control was specifically improved under these circumstances with doses on the order of 64–68 Gy compared with doses on the order of 60 Gy. Higher dose, however, did not completely abrogate the adverse effect of positive margins. Conclusion After gross total resection, soft tissue sarcoma with features predictive of a higher than average local recurrence rate benefited from doses of 64–68 Gy compared with 60 Gy.