Localized High-grade Soft Tissue Sarcoma Research Articles

Non-invasive monitoring of neoadjuvant radiation therapy response in soft tissue sarcomas by multiparametric MRI and quantification of circulating tumor DNA-A study protocol.

Wide resection remains the cornerstone of localized soft-tissue sarcomas (STS) treatment. Neoadjuvant radiation therapy (NRT) may decrease the risk of local recurrences; however, its effectiveness for different histological STS subtypes has not been systematically investigated. The proposed prospective study evaluates the NRT response in STS using liquid biopsies and the correlation of multiparametric magnetic resonance imaging (mpMRI) with histopathology and immunohistochemistry. Patients with localized high-grade STS, who qualify for NRT, are included in this study. Quantification of circulating tumor DNA (ctDNA) in patient blood samples is performed by targeted next-generation sequencing. Soft-tissue sarcoma subtype-specific panel sequencing in combination with patient-specific exome sequencing allows the detection of individual structural variants and point mutations. Circulating free DNA is isolated from peritherapeutically collected patient plasma samples and ctDNA quantified therein. Identification of breakpoints is carried out using FACTERA. Bioinformatic analysis is performed using samtools, picard, fgbio, and the MIRACUM Pipeline. Combination of conventional MRI sequences with diffusion-weighted imaging, intravoxel-incoherent motion, and dynamic contrast enhancement. Multiparametric MRI is performed before, during, and after NRT. We aim to correlate mpMRI data with the resected specimen's macroscopical, histological, and immunohistochemical findings. Preliminary data support the notion that quantification of ctDNA in combination with tumor mass characterization through co-registration of mpMRI and histopathology can predict NRT response of STS. The methods presented in this prospective study are necessary to assess therapy response in heterogeneous tumors and lay the foundation of future patient- and tumor-specific therapy concepts. These methods can be applied to various tumor entities. Thus, the participation and support of a wider group of oncologic surgeons are needed to validate these findings on a larger patient cohort.

Photon and Proton irradiation in Patient-derived, Three-Dimensional Soft Tissue Sarcoma Models

BackgroundDespite their heterogeneity, the current standard preoperative radiotherapy regimen for localized high-grade soft tissue sarcoma (STS) follows a one fits all approach for all STS subtypes. Sarcoma patient-derived three-dimensional cell culture models represent an innovative tool to overcome challenges in clinical research enabling reproducible subtype-specific research on STS. In this pilot study, we present our methodology and preliminary results using STS patient-derived 3D cell cultures that were exposed to different doses of photon and proton radiation. Our aim was: (i) to establish a reproducible method for irradiation of STS patient-derived 3D cell cultures and (ii) to explore the differences in tumor cell viability of two different STS subtypes exposed to increasing doses of photon and proton radiation at different time points.MethodsTwo patient-derived cell cultures of untreated localized high-grade STS (an undifferentiated pleomorphic sarcoma (UPS) and a pleomorphic liposarcoma (PLS)) were exposed to a single fraction of photon or proton irradiation using doses of 0 Gy (sham irradiation), 2 Gy, 4 Gy, 8 Gy and 16 Gy. Cell viability was measured and compared to sham irradiation at two different time points (four and eight days after irradiation).ResultsThe proportion of viable tumor cells four days after photon irradiation for UPS vs. PLS were significantly different with 85% vs. 65% (4 Gy), 80% vs. 50% (8 Gy) and 70% vs. 35% (16 Gy). Proton irradiation led to similar diverging viability curves between UPS vs. PLS four days after irradiation with 90% vs. 75% (4 Gy), 85% vs. 45% (8 Gy) and 80% vs. 35% (16 Gy). Photon and proton radiation displayed only minor differences in cell-killing properties within each cell culture (UPS and PLS). The cell-killing effect of radiation sustained at eight days after irradiation in both cell cultures.ConclusionsPronounced differences in radiosensitivity are evident among UPS and PLS 3D patient-derived sarcoma cell cultures which may reflect the clinical heterogeneity. Photon and proton radiation showed similar dose-dependent cell-killing effectiveness in both 3D cell cultures. Patient-derived 3D STS cell cultures may represent a valuable tool to enable translational studies towards individualized subtype-specific radiotherapy in patients with STS.

The role of neoadjuvant radiochemotherapy in the management of localized high-grade soft tissue sarcoma

BackgroundStandard treatment of soft tissue sarcoma (STS) of the extremities includes limb-sparing surgery combined with pre- or postoperative radiotherapy (RT). The role of perioperative chemotherapy (CTX) remains uncertain. STS patients with high-risk features for local recurrence, distant metastases, and increased mortality may require additional systemic therapy. The objective of this study was to evaluate predictors of outcome regarding local control (LC), overall survival (OS), and freedom from distant metastases (FFDM) in a large single-center cohort of patients suffering from localized high-grade STS (grade 2/3, G2/G3). Special emphasis was put on a subgroup of patients who received combined neoadjuvant radiochemotherapy (RCT).MethodsOverall, 115 adult STS patients were included in this retrospective study. The median follow-up was 34 months. Twenty-three patients (20.0%) were treated with neoadjuvant RCT, 92 (80.0%) received other therapies (adjuvant RT alone (n = 58); neoadjuvant CTX + adjuvant RT (n = 17); adjuvant RCT (n = 10), neoadjuvant RT alone (n = 7)). To assess potential prognostic factors on LC, OS, and FFDM, univariate (UVA) and multivariable (MVA) Cox proportional hazards models were applied.ResultsUVA showed significantly better LC rates in the neoadjuvant RCT group (p = 0.025), with trends in MVA (p = 0.057). The 3-year LC rate was 89.7% in the neoadjuvant RCT group vs. 75.6% in the "other therapies" group. UVA also showed significantly better OS rates in the neoadjuvant RCT group (p = 0.049), however, this was not confirmed in MVA (p = 0.205), the 3-year OS rate was 85.8% for patients treated with neoadjuvant RCT compared to 73.5% in the "other therapies" group. UVA showed significantly better FFDM rates in (p = 0.018) and a trend towards better FFDM rates in MVA (p = 0.059). The 3-year FFDM rate was 89.7% for patients treated with neoadjuvant RCT compared to 65.9% in the "other therapies" group. In the subgroup of patients with G3 STS, neoadjuvant RCT was a significant positive predictor of LC and FFDM in MVA (p = 0.047, p = 0.027) but not for OS. Overall grade 3 and 4 toxicities were significantly higher (p = 0.019) in the neoadjuvant RCT group and occurred in 73.9% vs. 38.0% in patients receiving other therapies.ConclusionsThe results suggest that neoadjuvant RCT might improve LC and FFDM in patients with localized G3 STS while also being associated with increased acute complication rates. Further prospective research is warranted to confirm these findings.

Patients with an increased time to treatment initiation have a poorer overall survival after definitive surgery for localized high-grade soft-tissue sarcoma in the extremity or trunk

Time to treatment initiation (TTI) is generally defined as the time from the histological diagnosis of malignancy to the initiation of first definitive treatment. There is no consensus on the impact of TTI on the overall survival in patients with a soft-tissue sarcoma. The purpose of this study was to determine if an increased TTI is associated with overall survival in patients with a soft-tissue sarcoma, and to identify the factors associated with a prolonged TTI. We identified 23,786 patients from the National Cancer Database who had undergone definitive surgery between 2004 and 2015 for a localized high-grade soft-tissue sarcoma of the limbs or trunk. A Cox proportional hazards model was used to examine the relationship between a number of factors and overall survival. We calculated the incidence rate ratio (IRR) using negative binomial regression models to identify the factors that affected TTI. Patients in whom the time to treatment initiation was prolonged had poorer overall survival than those with a TTI of 0 to 30 days. These were: 31 to 60 days (hazard ratio (HR) 1.08, p = 0.011); 61 to 90 days (HR 1.11, p = 0.044); and 91 days (HR 1.22; p = 0.003). The restricted cubic spline showed that the hazard ratio increased substantially with a TTI longer than 50 days. Non-academic centres (vs academic centres; IRR ranging from 0.64 to 0.86; p < 0.001) had a shorter TTI. Those insured by Medicaid (vs private insurance; IRR 1.34), were uninsured (vs private insurance; IRR 1.17), or underwent a transition in care (IRR 1.62) had a longer TTI. A time to treatment initiation of more than 30 days after diagnosis was independently associated with poorer survival. The hazard ratio showed linear increase, especially if the TTI was more than 50 days. We recommend starting treatment within 30 days of diagnosis to achieve the highest likelihood of cure for localized high-grade soft-tissue sarcomas in the limbs and trunk, even when a patient needs to be referred to a specialist centre. Cite this article: Bone Joint J2021;103-B(6):1142-1149.

Chemotherapy improves distant control in localized high-grade soft tissue sarcoma of the extremity/trunk

BackgroundSoft tissue sarcomas (STS) are rare and heterogeneous tumors making chemotherapy use controversial. Our goal was to identify a subset of patients with primary STS that benefit with the addition of chemotherapy.MethodsA retrospective chart review included intermediate to high-grade localized primary STS of the extremity/trunk, and tumor size > 5 cm. The effect of chemotherapy was evaluated for local control (LC), distant control (DC), progression free survival (PFS), and overall survival (OS).ResultsIn this cohort (n = 273), patients were treated with surgery (98%), radiation (81%), and chemotherapy (24.5%). With a median follow-up of 51 months, the entire cohort’s 5-year LC, DC, PFS, and OS are 79.1%, 59.9%, 43.8%, and 68.7%, respectively. The addition of chemotherapy did not provide a DC benefit (p = 0.238) for the entire cohort. High-grade disease (n = 210) experienced a 5-year benefit in DC (68% vs. 54.4%, p = 0.04), which was more pronounced with MAI (Mesna, Adriamycin, Ifosfamide) based regimens (74.2%, p = 0.016), and a 5-year PFS (50.8% vs 45%, p = 0.025) and OS benefit (76.2% vs 70%, p = 0.067) vs. no chemotherapy. On multivariate analysis of the high-grade subset, chemotherapy independently predicted for a DC benefit (HR 0.48 95% CI 0.26–89, p = 0.019). The benefit of chemotherapy was more pronounced with MAI, showing a significant benefit in DC (HR 0.333 95% CI 0.145–0.767, p = 0.01) and PFS (HR 0.52 95% CI 0.28–0.99, p = 0.047).ConclusionIn patients with localized STS > 5 cm, the high-grade subset had a distant control benefit with the addition of chemotherapy, leading to improved progression free survival. This is more pronounced with the use of MAI and should be considered in patients eligible for this regimen.

The use of radiation therapy in localized high-grade soft tissue sarcoma and potential impact on survival.

It is a consensus that radiation therapy (RT) should be applied for all large, deep, high-grade soft tissue sarcomas (STS). Therefore, we investigated the National Cancer Database (NCDB) to study how these guidelines are being followed, to determine what factors may be associated with the decision not to use RT, and to see whether there was an association of RT use and survival. We retrospectively analyzed localized high-grade STS patients in the NCDB from 1998 through 2006. They were further stratified into two groups: no radiation (NRT) group and radiation (RT) group. Then, long-term survival between the two groups was evaluated using the Kaplan-Meier (KM) method with comparisons based on the log-rank test. Multiple variables were analyzed between the two groups. Propensity matching was performed secondarily to minimize the influence of confounding variables. A total of 3982 of 10,290 patients (37.8 %) did not receive RT and 6,308 patients (62.2 %) did receive RT. Patients in the NRT group were more likely to have a below-median education level (median 58.2 % vs. 60.7 %; p = 0.015) and a below-median income level (65.1 % vs. 68.6 %; p < 0.001). In addition, these patients lived farther from their treatment centers (20.2 vs. 14.8 miles, p = 0.002) and were more likely to be uninsured (5.3 % vs. 3.5 %, p < 0.001). They were less likely to receive a radical excision (55.2 % vs. 70.1 %; p < 0.001) and more likely to receive amputation (20.9 % vs. 3.3 %; p < 0.001). The 30-day mortality (1.2 % vs. 0.2 %; p < 0.001) and readmission rate (3.8 % vs. 2.8 %; p = 0.031) were higher for the NRT group. KM analysis showed that long-term survival for patients who did not receive RT was significantly lower, even after propensity score matching (p < 0.001). This large database review reveals a striking lack of utilization of RT to treat high-grade STS, which correlates with poorer survival even after propensity matching. Lower education and income levels and diminished access to medical care (insurance and distance to the facility) are associated with failing to receive RT.

Doxorubicin-based adjuvant chemotherapy in soft tissue sarcoma: pooled analysis of two STBSG-EORTC phase III clinical trials

The EORTC-STBSG coordinated two large trials of adjuvant chemotherapy (CT) in localized high-grade soft tissue sarcoma (STS). Both studies failed to demonstrate any benefit on overall survival (OS). The aim of the analysis of these two trials was to identify subgroups of patients who may benefit from adjuvant CT. Individual patient data from two EORTC trials comparing doxorubicin-based CT to observation only in completely resected STS (large resection, R0/marginal resection, R1) were pooled. Prognostic factors were assessed by univariate and multivariate analyses. Patient outcomes were subsequently compared between the two groups of patients according to each analyzed factor. A total of 819 patients had been enrolled with a median follow-up of 8.2 years. Tumor size, high histological grade and R1 resection emerged as independent adverse prognostic factors for relapse-free survival (RFS) and OS. Adjuvant CT is an independent favorable prognostic factor for RFS but not for OS. A significant interaction between benefit of adjuvant CT and age, gender and R1 resection was observed for RFS and OS. Males and patients >40 years had a significantly better RFS in the treatment arms, while adjuvant CT was associated with a marginally worse OS in females and patients <40 years. Patients with R1 resection had a significantly better RFS and OS favoring adjuvant CT arms. Adjuvant CT is not associated with a better OS in young patients or in any pathology subgroup. Poor quality of initial surgery is the most important prognostic and predictive factor for utility of adjuvant CT in STS. Based on these data, we conclude that adjuvant CT for STS remains an investigational procedure and is not a routine standard of care.

A Probabilistic Analysis of Completely Excised High-grade Soft Tissue Sarcomas of the Extremity: An Application of a Bayesian Belief Network

It is important to understand the relative importance of prognostic variables in patients with soft tissue sarcomas. The purpose of this study was to describe the hierarchical relationships between features inherent to completely excised, localized high-grade soft tissue sarcomas of the extremity and compare the associations to those previously reported. Data were collected from the Memorial Sloan-Kettering Cancer Center Sarcoma Database. All adult patients with high-grade extremity soft tissue sarcomas who underwent complete excision (R0 margins) at our institution between 1982 and 2010 were included in the analysis. Bayesian belief network (BBN) modeling software was used to develop a hierarchical network of features trained to estimate the likelihood of disease-specific survival. Important relationships depicted by the BBN model were compared to those previously reported. The records of 1318 consecutive patients met the inclusion criteria, and all were included in the analysis. First-degree associates of disease-specific survival were the primary tumor size; presence of and time to distant recurrence; and presence of and time to local recurrence. On cross-validation, the BBN model was sufficiently robust, with an area under the curve of 0.94 (95 % confidence interval 0.93-0.96). We successfully described the hierarchical relationships between features inherent to patients with completely excised high-grade soft tissue sarcomas of the extremity. The relationships defined by the BBN model were similar to those previously reported. Cross-validation results were encouraging, demonstrating that BBN modeling can be used to graphically illustrate the complex hierarchical relationships between prognostic features in this setting.

Radiological tissue changes and pathological response in localized high-grade soft tissue sarcomas (STS) as predictors of outcome after neoadjuvant treatment with chemoradiotherapy (CRT).

10095 Background: Neoadjuvant CRT has demonstrated efficacy in the treatment of locally advanced STS. We analyzed the relation between radiological and pathological changes in the response and outcome after concurrent preoperative chemotherapy and radiation therapy (RT) in localized high-grade STS. Methods: Between 2001 and 2006, 22 patients with localized high-risk STS of extremities or superficial trunk received 3 cycles of neoadjuvant epirubicin + ifosfamide and concomitant RT, followed by surgery, within a prospective phase III trial. MRI were performed before and after the neoadjuvant treatment. Changes in tumor size, tissue characteristics (T1/T2), and contrast enhancement variations were recorded. Pathological changes were analyzed in the surgical specimen and correlated with radiological response patterns, and post-treatment changes (necrosis, hemorrhage, tumor viability, tumor cell distribution). Results: According to RECIST, 6 patients (27%) had a PR, 14 patients (63%) SD and 2 patients had a PD confirmed histologically, in terms of more than 50% of residual vial tumor cells. 3 patients had a RECIST SD, and pathologically, there was more than 50% of residual tumour in all surgical specimens. Other 5 (23%) patients had a RECIST SD with radiographic signs of tissue changes (T1 hiperintensity): pathologically, the residual tumour was less than 50% in all. Another 10 patients with PR/SD showed radiological changes (size and T1) and pathological response > 50%; 1 patient with a RECIST SD had radiological signs of tissue progression confirmed histologically with the presence of the 95% of vial tumor cells in the surgical specimen. Tumor size reduction has prognostic significance (p 0.04); Tumor necrosis and positive margins didn't have prognostic value. Radiological change to hiperintensity in T1 was the only statistically significant change for overall survival (p 0.002). Conclusions: Tumor size and some tissue response criteria on MRI may predict pathological tissue responses, helping RECIST criteria, in order to establish prognosis in high-grade STS treated with preoperative chemoradiotherapy. No significant financial relationships to disclose.

Neoadjuvant treatment evaluation in soft tissue sarcomas (STS): Looking for news in radiologic and pathologic response.

e20509 Background: Chemotherapy (CT) and combined chemoradiotherapy (CRT) have been explored for preoperative management of locally advanced soft tissue sarcomas (STS). Pathological and radiological changes could be a predictor of behaviour and predictor factor in STS. Objective: To correlate pathological and radiological patterns of response to neoadjuvant chemotherapy (CT) or chemoradiotherapy (CRT) in localized high grade STS. Methods: Between 2001 and 2009, 34 patients stage III STS were treated in two consecutive neoadjuvant trials with high-dose ifosfamide or epirubicine + ifosfamide (22 patients received CRT 44 Gy) before surgery (70% conservative surgery). Adjuvant treatment consisted in CT in 13 p (4 high- dose ifosfamide, 9 ifosfamide-epirrubine) and RT in 10 p. Median follow-up was 33 months (4.2-99). Histological types: 15 pleomorphic, 8 synovial, 4 leiomiosarcoma, 7 others. Median tumor size 11cm (5-25cm). Patients were evaluated with MRI basal and before surgery, analizing size, necrosis, contrast uptake and signal (T1 and T2). Pathological response includes size, margins, tumor viability, distribution and necrosis (according Huvos score). Results: Response rate (RECIST) was PR 12 p (36%), SD 19 p (57%), PD 2 p (6%) and it correlates with survival (p 0.03). Overall survival was 83.6m (1,2,3-year survival: 97.1%, 89.6%, 78.4% respectively). Disease-free survival (DFS) was 78.29m (65.28-91.30). Induced tumoral necrosis (≥95%) after treatment didn't show statistical significance. Positive margins (p 0.03) and size increase (p 0.017) correlates with worse prognosis. Only T1 signal change to hiperintensity was significant with better survival (p 0.001), relapse (p 0.02) and time to relapse (p 0.004); decrease in contrast uptake was not significant. Conclusions: After neoadjuvant treatment in STS, analizing MRI tumor size and T1 signal changes to hiperintensity should be considered in response evaluation. Optimal surgery should include negative margins. However tissue necrosis does not seem to predict outcome. No significant financial relationships to disclose.

The end of adjuvant chemotherapy (adCT) era with doxorubicin-based regimen in resected high-grade soft tissue sarcoma (STS): Pooled analysis of the two STBSG-EORTC phase III clinical trials

10525 Background: The EORTC STBSG has coordinated the two largest trials of adCT vs no adCT in localized high grade STS. In both studies adCT failed to demonstrate any benefit on overall survival (OS). The aim of this analysis was to identify subgroups of patients who benefit more from adjuvant CT than others. Methods: We pooled individual patient (pt) data from two EORTC trials comparing adCT (CYVADIC in 62771 and AI in 62931) to a control arm in completely resected STS (R0 or R1) to identify prognostic factors, by univariate and a multivariate analysis. The outcome of pts (OS or PFS) was subsequently compared between the two groups of pts according to each investigated factor. Results: A total of 819 pts were included, with a median follow-up of 8.2 years (62771 trial: 468 pts, 9.7 yrs; 62931 trial: 351 pts; 6.6 yrs). Large tumor size, high histologic grade and R1 resection are independent adverse prognostic factors for both PFS and OS. AdCT is an independent favourable prognostic factor for PFS but not for OS. A significant interaction between the benefit of adCT and age, sex and R1 resection was observed for both PFS and OS. Tumor size, histologic subtype and grade were not associated with any PFS or OS benefit for adCT. Males had a significantly better PFS but not OS in the adCT arms, pts older than 40 yrs had a significantly better PFS in the adCT (while adCT was associated with a marginally (p=0.08) worse OS in pts<40). Pts with R1 resection had a significantly better PFS and OS in the adCT arms. Conclusions: This study confirms previously documented prognostic factors in completely resected STS. Contrary to our initial hypothesis, adCT is not associated with a better outcome in young pts or any pathological subgroup. Quality of initial surgery is the most important prognostic and predictive factor for utility of adCT for PFS and OS. No significant financial relationships to disclose.

Patterns of recurrence in patients with high-grade soft-tissue sarcomas.

From July 1975 to December 1982, 563 patients were referred to the Surgery Branch of the National Cancer Institute with the diagnosis of soft-tissue sarcoma. Three hundred and seven of these patients had fully resectable, localized high-grade soft-tissue sarcomas and were treated at the National Cancer Institute using standard protocols with surgery alone, or in combination with chemotherapy and/or radiotherapy. An aggressive surgical approach was undertaken in the management of patients who subsequently developed recurrent disease. These 307 cases have been reviewed, with a median duration of follow-up of 30 months, to determine the frequency of recurrent disease, the patterns of recurrence, and the impact of surgery on the survival of patients who developed recurrent disease. Disease recurred in one hundred seven patients (107/307, 35%), with a median disease-free interval of 18 months (range, 0.5 to 72.0 months). The frequency of recurrence by site of primary sarcoma was extremity, 31% (65/211); head and neck, 33% (4/12); trunk, 40% (17/42); retroperitoneum, 47% (17/36); and breast, 67% (4/6). Isolated pulmonary metastatic disease was the most common pattern of initial recurrence (56/107, 52%) followed by isolated local recurrence (21/107, 20%). Single other sites of recurrence and multiple concurrent sites of recurrence each accounted for 14% (15/107) of all initial recurrences. The relative frequency of each of these four patterns of recurrence varied with the site of the primary sarcoma. The outcome for patients with recurrent disease depended on the site of recurrence, rather than on the site of the primary sarcoma. Sixty-six patients (66/107, 62%) with recurrent disease were rendered surgically disease-free with the first recurrence, including 40 (40/56, 72%) patients with isolated pulmonary metastases, 20 patients (20/21, 96%) with isolated local recurrences, five patients (5/15, 33%), with isolated other sites of recurrence and one patient (1/15, 7%) with multiple sites of initial recurrence. Following surgical resection, the actuarial three-year survival for the 66 patients rendered disease-free was 51%. The median survival for the 41 patients not rendered surgically disease-free with the first recurrence was only 7.4 months. Thirty of the sixty-six patients (30/66, 45%) rendered disease-free with the first recurrence remained disease-free at follow-up, with a median follow-up of 28 months from the time of resection of the first recurrence. The remaining 36 patients (36/66, 55%) subsequently recurred, with a median disease-free interval of 7.3 months.(ABSTRACT TRUNCATED AT 400 WORDS)

Survival of patients with localized high-grade soft tissue sarcoma with multimodality therapy. A matched control study.

Ten of 16 consecutive patients (63%) with Stages III-IVA soft tissue sarcoma presenting between 1975 and 1978 and treated with surgery, radiotherapy and adjuvant chemotherapy have remained disease-free with a median follow-up of three years (range, 28-68 months). Survival at three years was 86%. However, in the American Joint Committee (AJC) soft tissue sarcoma staging system published in 1977, Grade 3 soft tissue sarcomas were associated with a three-year survival of 35% and almost 90% of the patients destined to fail did so within three years of diagnosis (8). To determine if the observed improvement in survival resulted merely from lesions with favorable prognostic determinants at diagnosis, study patients were matched for stage, histologic type and location of the primary lesion with controls generated from these 1215 carefully reviewed sarcoma patients collected from the data base of the Task Force on Soft Tissue Sarcomas of the AJC. Only control cases whose histology had been reviewed and who had been treated with surgery (with or without radiotherapy) were included in the analysis. Cases survived significantly longer than controls at three years (p less than 0.001) and, in fact, disease-free survival of cases (63%) was superior to overall survival of controls (27%) (p less than 0.01). Our data support the conclusion that patients with high-grade soft tissue sarcoma treated by an experienced multimodality team have a three-year disease-free survival of approximately 63%. The impact of each component of multimodality therapy cannot be determined, and improved survival may result, in addition, from improved diagnostic and staging techniques currently available.

Feasibility of combined modality therapy for localized high-grade soft tissue sarcomas in adults

Seventeen consecutive patients with localized, high grade soft tissue sarcomas had resection of their primary tumor, radiation therapy and chemotherapy. The soft tissue sarcoma was primary in 14 patients and regionally recurrent in 3 patients. Chemotherapy consisted of cyclophosphamide 500 Mg/M 2 day 1, Adriamycin (ADR) 60 mg/M 2 day 2, and DTIC 400 Mg/M 2 days 1 and 2, given every 21 days to a maximum ADR dose of 450 mg/M 2. Cyclophosphamide and DTIC were then given to a total duration of 1 year. Radiation therapy consisted of 4000–5000 rad by megavoltage photons in 5 weeks, and in selected cases, an additional 1500–2000 rad by electron beam boost in the tumor bed delivered over 2 additional weeks. Following surgery, 12 patients were treated sequentially with an interval of chemotherapy, radiation therapy and then the completion of chemotherapy. The added morbidity of this sequential approach is minimal: one patient of 12 had delayed primary healing of her wound, 1 of 10 patients required a break in radiation therapy because of skin erythema. Four patients were treated with intensive pre-chemotherapy radiation therapy because of inadequate surgical margins. The median time on study was 18 months from onset of treatment (range, 8–41 months). Although there have been no local, regional or distant recurrences, the follow-up time is inadequate to assess the therapeutic benefit of this combined modality treatment.