High-grade Extremity Soft Tissue Research Articles

The incidence, risk factors and outcomes of wound complications after preoperative radiotherapy and surgery for high grade extremity soft tissue sarcomas: A 14-year retrospective study

ObjectiveThe aim of this study was to analyze the wound complication (WC) rate and to determine the risk factors for WC in patients with soft tissue sarcoma treated with preoperative radiotherapy followed by surgical resection. MethodsUsing the database of Oxford University Hospital (OUH) we retrospectively studied 126 cases of soft tissue sarcomas treated with preoperative radiotherapy and surgery between 2007 and 2021. WC were defined as minor wound complication (MiWC) not requiring surgical intervention or major wound complication (MaWC) if they received a secondary surgical intervention. Univariate and multiple regression analyses were performed using frequency of WC and MaWC as a dependent variable. ResultsThe incidence of WC and MaWC was 43.7% (55/126) and 19% (24/126). Age (OR:1.03, 95%CI: 1.00–1.06, p = 0.016), tumor size (OR:1.11, 95%CI:1.01–1.21, p = 0.027) and tumor site namely proximal lower limb vs upper limb (OR:10.87, 95%CI 1.15–103.03, p = 0.038) were risk factors on multivariate analysis. In nested case control analysis, the incidence of MaWC was 43.6% (24/55), the mean recovery time is 143 days in patients with MaWC. Smoking increases the risk for MaWC (OR:8.32, 95%CI:1.36–49.99, p = 0.022). The time interval between surgery and wound complication reduces the risk for MaWC (OR:0.91, 95%CI:0.84–0.99, p = 0.028) in multivariate analysis. ConclusionsAge, tumor site and size are risk factors for WC requiring preoperative radiotherapy. Smoking and the time interval between surgery and wound complication are risk factors for MaWC as compared with MiWC. MaWC rate (19%) are comparable to those in postoperative radiotherapy and surgery alone.

Growth factor and its role in the treatment of patients with soft tissue extremity sarcoma receiving chemotherapy managed at an academic center: A retrospective study.

e23573 Background: Surgery still remains the mainstay of treatment with curative intent for high grade extremity soft tissue non rhabdomyosarcoma sarcomas (HG ESTS). Adjuvant/neoadjuvant Chemotherapy (CT) is still debatable, but most experts agree about its role in HG-ESTS in combination with radiation (R). Interdigitated CT+R is an attractive method of delivering these modalities of treatment in short time prior to surgery, however safety of using growth factor (GF) while administering CT+R in HG ESTS is largely unknown. We conducted a retrospective study of the toxicities associated with GF administration in this setting at a single institution. Methods: Electronic medical records at one institution were reviewed to identify patients having a diagnosis of extremity STS between October 2017- January 2020. Demographics, details of tumor characteristics, and treatment details were noted. Details of Interdigitated (ID)CRT were noted; the intended CT regimen was doxorubicin/ifosphamide/mesna (MAI) at 100% of the intended dosing. Data regarding the toxicities associated with GF administration were also evaluated in these patients; specifically, the development of febrile neutropenia, thrombocytopenia and pulmonary toxicity were evaluated. Patients who presented with metastatic disease were excluded from this analysis. Results: 22 patients were identified. Median age was 63 years. Of these, 9 patients (40%) were smokers. At diagnosis, 6 patients (27%) had metastatic disease. The most common site of primary disease was the thigh (50%). The most common histology was undifferentiated pleomorphic sarcoma (59%). CT monotherapy was administered in 3 patients. RT was administered in 14 patients, out of whom interdigitated CRT was administered in 10 patients. 60% of patients who initiated were able to receive 3 cycles of ID-CRT prior to Surgery. GF was administered in 14 patients who received regimens including CT. Of patients receiving ID-CRT who received GF, 60% completed ID-CRT without delays. No delays occurred due to thrombocytopenia. Febrile neutropenia occured in 22% of patients who received GF. Only 1 patient who received GF suffered prolonged thrombocytopenia. No patients who received GF were noted to have pulmonary toxicity. Conclusions: For adults with HG ESTS, GF administration with ID-CRT does not appear to cause any additional delay in treatment due to prolonged thrombocytopenia or lung toxicity. Inclusion of GF administration in further prospective trials of ID-CRT appears feasible.

Preoperative Intensity-Modulated Radiation Therapy Compared to Three-Dimensional Conformal Radiation Therapy for High Grade Extremity Sarcomas in Children: An Analysis of Children's Oncology Group (COG) Study ARST 0332

One of the potential disadvantages of neoadjuvant chemoradiation therapy for high grade extremity soft tissue sarcomas (STS) is an increased risk of peri-operative wound complications. In adults, studies have demonstrated reduced radiation dose to the skin and subcutaneous soft tissues may decrease the acute wound complication rate and lead to better limb function. Intensity modulated radiotherapy (IMRT) allows delivery of dose to the target volume with the potential advantage of highly conformal therapy to reduce dose to subcutaneous tissues thus limiting dose to the skin. The purpose of this study was to assess tumor coverage and skin dose in pediatric patients treated with IMRT vs. 3D conformal radiation therapy (3D-CRT) on ARST 0332. Of the 551 eligible patients, 200 were enrolled in Arm D of ARST 0332 in which patients <30 years of age were treated with neoadjuvant ifosfamide/doxorubicin chemotherapy and 45 Gy RT, then surgery, and an RT boost based on margins. A total of 121 RT plans of patients were available for review through remote access of the Imaging and Radiation Oncology Core (IROC) Rhode Island database. Of these, 56 RT plans for patients with extremity STS were reviewed to evaluate the dose delivered to the clinical target volume (CTV) and skin (contoured from the surface to a depth of 5 mm). Of the 56 pediatric patients with extremity STS with RT plans available for review, 38 (65%) were treated with 3D-CRT and 18 (32%) with IMRT. There was no difference in distribution of site treated with IMRT vs. 3D-CRT (upper leg: 53% vs. 50%; knee: 16% vs. 17%; lower leg: 11% vs. 17%; lower arm: 11% vs. 17%, IMRT vs. 3D-CRT, respectively) with the exception of 0% vs. 11% of patients treated with IMRT vs. 3D-CRT to the upper arm. There was no difference in CTV volume between groups of patients treated with IMRT (median 1027 cc, range 66-2867 cc) or 3D-CRT (median 647 cc, range 30-4854 cc) (P = 0.920); however, patients treated with IMRT had significantly improved CTV coverage with 100% of the prescription dose compared to those receiving 3D-CRT (median CTV coverage, 95% vs. 87% respectively, P = 0.011). In patients without skin bolus, the percentage of skin receiving 45 Gy or more was significantly lower in patients treated with IMRT compared to 3D-CRT (mean percentage, 3% vs. 8% respectively, P = 0.039). Pre-operative IMRT compared to 3D-CRT may result in improved RT target coverage with reduced dose to the skin. Future studies are important to assess if this lower skin dose translates to reduced wound complications and/or improved limb function.

A retrospective risk assessment of patients (pts) with high grade upper (UE) and lower extremity (LE) sarcoma: Predictors of survival.

e21504 Background: Patient outcomes of high grade extremity soft tissue sarcomas (STS) are dependent upon grade and size of the primary tumor and extent of surgical resection. Poorer overall survival (OS) has been associated with specific anatomic sites (e.g. head and neck, retroperitoneum) but OS has not been evaluated for UE vs LE. We investigated the relationship of tumor size and anatomic sites with OS in our pts with high grade extremity STS. Methods: A retrospective review of all pts diagnosed with a high grade STS of the UE and LE was performed from 1992-2010 via an IRB approved protocol at Levine Cancer Institute. Pts were included if they had sufficient medical records, limb-sparing surgery, age greater than 18 years, no stage IV disease. All cases were centrally reviewed by a single pathologist. Overall survival was analyzed with Cox proportional hazards models and tumor size was analyzed using ANOVA techniques. Results: 93 pts were identified. 61 pts had LE sarcomas and 32 had UE. Demographics: 52% male, 67% Caucasian, 60% &gt;50 years of age. Disease characteristics included 88% deep and 66% &gt;5cm STS. 13% of pts received chemotherapy and 86% received radiation therapy, consistent with NCCN guidelines and institutional protocol. Median baseline tumor size was 7.0 cm with a range of 1.7-40 cm. LE STS were generally larger than UE; medians 8.5 cm (range 1.7-40 cm) vs 5.0 cm (range 2.0-17 cm), p=0.005. When analyzed quantitatively, larger tumor size correlated with an increased risk of death (p=0.001). 28 total deaths occurred (0.3-5.4 yrs). Death rates were 27.9% (17 deaths) with LE STS vs 34.4% (11 deaths) with UE. LE disease had an overall reduced risk of death (HR=0.543). Pts with tumors &gt;5cm had an increased risk of death (HR=3.235 overall) for both LE (HR=3.042) and UE (HR=3.453) sarcomas. Conclusions: To our knowledge, this is the largest reported cohort of high grade STS that stratified on upper and lower extremities. Larger size was associated with higher risk of death. Additionally, we observed a higher risk of death in patients with UE sarcomas vs. LE sarcomas. Strong consideration should be given to UE vs. LE STS when assessing risk and treatment.

Accuracy of real time noninvasive temperature measurements using magnetic resonance thermal imaging in patients treated for high grade extremity soft tissue sarcomas

To establish accuracy of real time noninvasive temperature measurements using magnetic resonance thermal imaging in patients treated for high grade extremity soft tissue sarcomas. Protocol patients with advanced extremity sarcomas were treated with external beam radiation therapy and hyperthermia. Invasive temperature measures were compared to noninvasive magnetic resonance thermal imaging (MRTI) at 1.5 T performed during hyperthermia. Volumetric temperature rise images were obtained using the proton resonance frequency shift (PRFS) technique during heating in a 140 MHz miniannular phased array applicator. MRTI temperature changes were compared to invasive measurements of temperature with a multisensor fiber optic probe inside a #15 g catheter in the tumor. Since the PRFS technique is sensitive to drifts in the primary imaging magnetic field, temperature change distributions were corrected automatically during treatment using temperature-stable reference materials to characterize field changes in 3D. The authors analyzed MRT images and compared, in evaluable treatments, MR-derived temperatures to invasive temperatures measured in extremity sarcomas. Small regions of interest (ROIs) were specified near each invasive sensor identified on MR images. Temperature changes in the interstitial sensors were compared to the corresponding ROI PRFS-based temperature changes over the entire treatment and over the steady-state period. Nonevaluable treatments (motion/imaging artifacts, noncorrectable drifts) were not included in the analysis. The mean difference between MRTI and interstitial probe measurements was 0.91 degrees C for the entire heating time and 0.85 degrees C for the time at steady state. These values were obtained from both tumor and normal tissue ROIs. When the analysis is done on just the tumor ROIs, the mean difference for the whole power on time was 0.74 degrees C and during the period of steady state was 0.62 degrees C. The data show that for evaluable treatments, excellent correlation (deltaT < 1 degrees C) of MRTI-ROI and invasive measurements can be achieved, but that motion and other artifacts are still serious challenges that must be overcome in future work.

Efficacy and safety of administration of gemcitabine and docetaxel with radiation therapy in patients with high-grade soft tissue sarcoma

e21503 Background: Neo-adjuvant therapy of soft tissue sarcoma is not standardized. Anthracyclines (A) improve disease free and overall survival in high grade extremity soft tissue sarcomas measuring more than 5 cm. A and ifosfamide (I) therapy require inpatient administration and is associated with significant toxicities when administered in combination with RT. G in combination with D has been shown to prolong progression free and overall survival in patients with advanced or metastatic STS after progression on A and I, and in patients unable to receive the combination. The safety of administration of G with radiation is not known. We evaluated the safety of neo-adjuvant G and D in combination with RT in patients with STS. Methods: Retrospective analysis of subjects with high grade STS treated with RT and neo-adjuvant chemotherapy with G and D was conducted. G 600mg/m2 was administered on days 1 and 8 along with D 75 mg/m2 on day 8 for a total of 3 cycles. 2200 cGY RT was administered in 11 daily fractions between cycles 1 and 2 and between cycles 2 and 3. 72 hour gap was given between RT and chemotherapy. Chemotherapy was administered on outpatient basis. Efficacy was evaluated by the extent of tumor necrosis at the time of surgery. Safety was evaluated by the presence of complications following chemotherapy. Results: GD + R was administered to 12 patients in the neo-adjuvant setting. 11 of them were evaluable for response. 10 of the 11 patients had evidence of tumor necrosis at the time of surgery. 1 patient had poor response. 3 of 11 patients had neutropenia complicating neo-adjuvant chemotherapy. 4 patients required hospital admission post chemotherapy. 3 for neutopenic fever, and 1 for fever, chills and pneumonia without neutropenia. Conclusions: Gemcitabine and taxotere combination with radiation therapy can be administered safely on outpatient basis with minimal toxicity. Further safety and efficacy evaluation of this therapy will need to be confirmed in a prospective phase II study. No significant financial relationships to disclose.

Ki-67 detected by MIB-1 predicts distant metastasis and tumor mortality in primary, high grade extremity soft tissue sarcoma.

Preoperative staging of localized extremely soft tissue sarcoma (STS) includes tumor grade, size, and depth. A positive microscopic margin (PMM) adds prognostic information postoperatively, which is not helpful for preoperative stratification into low and high risk groups. This study was undertaken to identify molecular markers associated with poor outcome that could be used to refine the preoperative staging of high grade extremity STS. Between January 1, 1983, and December 31, 1989, 1416 patients were entered into the STS prospective data base at the Memorial Sloan-Kettering Cancer Center. Of 232 patients identified with primary, high grade extremity lesions, 121 had tissue available for immunohistochemical (IHC) analysis. The clinicopathologic variables and molecular markers for the original 232 patients were correlated with those for the 121 patients analyzed in the current study. Overexpression of Ki-67, p53, and mdm2 and deletion of Rb were determined via standard IHC techniques on serial paraffin sections. Categoric overexpression was defined as > or = 20% nuclear staining. Continuous determination of the percentage of nuclear staining was also used for correlation with distant metastasis (DM) and tumor mortality (TM). Univariate and multivariate analyses were conducted with log rank and Wilcoxon tests and Cox regression analyses, respectively. The median follow-up was 64 months. Fifty-four of the 121 patients (45%) developed DM. Fifty-one of the 121 patients (42%) died of their disease. Factors found to be significant in univariate and multivariate analyses for both DM and TM were Ki-67 score, size, and PMM (all P values <0.05). Five year freedom from DM with a Ki-67 score of <20 was 70% versus 50% for a score. Overexpression of p53 of mdm2 or deletion of Rb did not correlate with increased risk of DM or TM alone or in combination with a Ki-67 score of > or = 20. In addition to standard preoperative criteria, Ki-67 score is an independent prognostic molecular marker that predicts DM and TM in high grade extremity STS. Selecting patients with high grade tumors for preoperative investigational treatment may be further refined according to whether the patients have Ki-67 score of > or = 20 and large tumor size.

Concepts in limb-sparing treatment of adult soft tissue sarcomas.

Pretreatment assessment of patients with soft tissue sarcomas of the extremities requires careful attention to a biopsy approach that will establish the precise diagnosis and will not compromise the subsequent definitive operative procedure. Also, staging procedures are required to evaluate the status of both local and distant sites. Limb-sparing surgery for high grade extremity soft tissue sarcomas is a feasible and appropriate approach in approximately 90% of patients with such lesions. Wide gross surgical margins around the sarcoma are the optimal operative approach. Circumstantial evidence is convincing that local treatment failure can be reduced by adjuvant regional radiation treatment when surgical margins are narrow, and end results appear to be equal to those obtained by more extensive surgical resection alone. Adjuvant radiation following operation with optimal gross surgical margins has not been established as adding benefit. Although some groups treating soft tissue sarcomas do use intraarterial chemotherapy in conjunction with these other modalities, there is, as yet, no convincing evidence that this aspect of the multimodality treatment adds to local and/or systemic disease control. The efficacy of adjuvant systemic chemotherapy for high grade soft tissue sarcomas remains to be established within the context of prospective clinical trials.