Treatment Of Soft Tissue Sarcomas Research Articles

Intraoperative photodynamic therapy in the combined treatment of soft tissue sarcoma

Soft tissue sarcoma is a rare malignant neoplasm. Despite the improvement of surgical techniques, the rate of relapses of the disease remains high. The search for alternative methods of treatment is relevant.Purpose. To evaluate safety and effectiveness of intraoperative photodynamic therapy of sarcoma in soft tissues.Material and methods. Forty-four patients with soft tissue sarcoma were included in the study. Patients were divided into three groups. Group 1 (n = 10): soft tissue sarcoma of stage T2-3N0M0G1, surgical treatment and intraoperative photodynamic therapy. Group 2 (n = 17): soft tissue sarcoma of stage T2-3N0M0G2-3, surgical treatment and intraoperative photodynamic therapy. Group 3 (n = 17): soft tissue sarcoma of stage T2-3N0M0-1G2-3, combined treatment – preoperative light therapy, surgical treatment, intraoperative photodynamic therapy, neoadjuvant and adjuvant chemotherapy. Fluorescence spectrometry was performed to determine the degree of photosensitizer accumulation in tumor tissue. Treatment methodology: photosensitizer was injected 2.5–3 hours before the surgery. The tumor was removed with resection of adjacent muscles and healthy tissues. Then, laser irradiation of the tumor bed was made using “Latus” device. Radiation power was up to 2,5 W, power density was up to 0,28 W/cm2, radiation dose was up to 100 J/cm2. Follow-up ranged from 14 to 44 months.Results. The spectrometry has revealed that photosensitizer was accumulated predominantly in tumor tissue. There were no reactions to photosensitizer injection, no changes in the tumor bed as well as no increase in wound healing period after intraoperative photodynamic therapy.Within the observation period, all patients stayed alive. Relapses of the disease were registered in 38.7 % of patients: in Group 1 – 30 %, in Group 2 – 35.3 %, in Group 3 – 53 %. Of the 20 patients with primary diagnosed neoplasms, relapses were seen in 30 %. Of the 24 patients with previously recurrent neoplasms, 45.8 % had repeated relapses.Conclusion. Intraoperative photodynamic therapy is a safe and effective technique for treating soft tissue sarcomas; it is also the promising direction for research. A small number of observations, a variety of histological forms and stages of the disease make it difficult to assess the effectiveness of the discussed approach. Further studies of intraoperative photodynamic therapy are required.

Leveraging homologous recombination repair deficiency in sarcoma.

Personalised oncology is at the forefront of cancer research. The goal of personalised oncology is to selectively kill cancer cells while minimising side effects on normal tissue. This can be achieved by identifying and targeting cancer vulnerabilities that distinguish it from normal cells. Many cancers are deficient in high-fidelity DNA repair pathways that maintain genomic stability, such as homologous recombination (HR). Such cancers are highly sensitive to targeted therapies that induce DNA damage or inhibit DNA repair pathways. A notable example and a poster child of personalised oncology are PARP1/2 inhibitors (PARPi) that selectively kill HR-deficient (HRD) cancer cells by preventing repair of DNA gaps or single-strand breaks (SSBs) (Slade, 2020). Inhibitors of cell cycle checkpoints such as CHK1 and WEE1 can also eliminate HRD cancers by pushing cancer cells through the cell cycle despite unrepaired DNA damage and causing death by mitotic catastrophe (Groelly etal, 2022). PARPi have been approved for the treatment of ovarian, breast, pancreatic, and prostate cancer but other cancer types with an HRD signature (HRDness) may also respond to PARPi treatment. Planas-Paz etal (2023) now show that many sarcomas show HRDness and respond to PARP1/2 and WEE1 inhibitors, thus offering a new personalised oncology approach for this treatment-refractory cancer.

Clinico-Demographic Profile Of Soft Tissue Sarcoma- 5 Year Experience From A Tertiary Care Centre Of Eastern India.

Soft tissue sarcomas (STS) are a diverse group of malignant mesenchymal neoplasm.But, due to their low prevalence, very little data is available worldwide as well as in India regarding their clinico-epidemiological pattern.In this study we analysed the clinico-demographic profile of STS patients attending a tertiary care centre of Eastern India over the last 5years. We analyzed the prospectively maintained database of a tertiary care centre of West Bengal in Eastern India, and collected the data regarding the demography, clinical profile, pathology and treatment of STS patients who attended our OPD between 2017-2021. The objective was to assess the demographic and clinical data of STS patients of Eastern India and compare it with those of the reported literature from rest of the country as well as outside world. Most of the cases (27%) were between 41-50years of age group with a slight male predominance (Male: Female = 1.01:1). Spindle cell sarcoma was the most common (24.3%) histology followed by undifferentiated pleomorphic sarcoma (15%) and extremities were the most common site of involvement (47.7%). 71% patients presented with stage III and advanced disease.81% patients underwent radical surgery,14% patient received neo-adjuvant and 60% received adjuvant radiotherapy.91% patients received systemic chemotherapy. To conclude, this study is one of its first from Eastern India and will act as a stepping stone for future studies concentrating on clinico-epidemiological profile, early diagnosis and treatment of STS.

New therapeutics for soft tissue sarcomas: Overview of current immunotherapy and future directions of soft tissue sarcomas.

Soft tissue sarcoma is a rare and aggressive disease with a 40 to 50% metastasis rate. The limited efficacy of traditional approaches with surgery, radiation, and chemotherapy has prompted research in novel immunotherapy for soft tissue sarcoma. Immune checkpoint inhibitors such as anti-CTLA-4 and PD-1 therapies in STS have demonstrated histologic-specific responses. Some combinations of immunotherapy with chemotherapy, TKI, and radiation were effective. STS is considered a 'cold', non-inflamed tumor. Adoptive cell therapies are actively investigated in STS to enhance immune response. Genetically modified T-cell receptor therapy targeting cancer testis antigens such as NY-ESO-1 and MAGE-A4 demonstrated durable responses, especially in synovial sarcoma. Two early HER2-CAR T-cell trials have achieved stable disease in some patients. In the future, CAR-T cell therapies will find more specific targets in STS with a reliable response. Early recognition of T-cell induced cytokine release syndrome is crucial, which can be alleviated by immunosuppression such as steroids. Further understanding of the immune subtypes and biomarkers will promote the advancement of soft tissue sarcoma treatment.

Targeted therapies for the treatment of soft tissue sarcoma.

Soft tissue sarcomas are rare malignant tumors derived from mesenchymal cells that have a high morbidity and mortality related to frequent occurrence of advanced and metastatic disease. Over the past two decades there have been significant advances in the use of targeted therapies for the treatment of soft tissue sarcoma. The ability to study various cellular markers and pathways related to sarcomagenesis has led to the creation and approval of multiple novel therapies. Herein, we describe the current landscape of targeted medications used in the management of advanced or metastatic soft tissue sarcomas, excluding GIST. We distinguish three categories: targeted therapies that have current US Food and Drug Administration (FDA) approval for treatment of soft tissue sarcoma, non-FDA approved targeted therapies, and medications in development for treatment of patients with soft tissue sarcoma.

The Next Frontier in Sarcoma: Molecular Pathways and Associated Targeted Therapies.

Soft tissue sarcomas (STS) are a rare, complex, heterogeneous group of mesenchymal neoplasms with over 150 different histological subtypes. Treatments for this malignancy have been especially challenging due to the heterogeneity of the disease and the modest efficacy of conventional chemotherapy. The next frontier lies in discerning the molecular pathways in which these mesenchymal neoplasms arise, metastasize, and develop drug-resistance, thereby helping guide new therapeutic targets for the treatment of STS. This comprehensive review will discuss the current understanding of tumorigenesis of specific STS subtypes, including oncogenic pathway alterations involved in cell cycle regulation, angiogenesis, NOTCH signaling, and aberrant genetic rearrangements. It will then review current therapies that have been recently developed to target these pathways, including a review of ongoing clinical studies for targeted sarcoma treatment, as well as discuss new potential avenues for therapies against known molecular pathways of sarcomagenesis.

Protocol for the 2ND-STEP study, Japan Clinical Oncology Group study JCOG1802: a randomized phase II trial of second-line treatment for advanced soft tissue sarcoma comparing trabectedin, eribulin and pazopanib

BackgroundSoft tissue sarcomas (STS) are a rare type of malignancy comprising a variety of histological diagnoses. Chemotherapy constitutes the standard treatment for advanced STS. Doxorubicin-based regimens, which include the administration of doxorubicin alone or in combination with ifosfamide or dacarbazine, are widely accepted as first-line chemotherapy for advanced STS. Trabectedin, eribulin, pazopanib, and gemcitabine plus docetaxel (GD), which is the empirical standard therapy in Japan, are major candidates for second-line chemotherapy for advanced STS, although clear evidence of the superiority of any one regimen is lacking. The Bone and Soft Tissue Tumor Study Group of the Japan Clinical Oncology Group (JCOG) conducts this trial to select the most promising regimen among trabectedin, eribulin, and pazopanib for comparison with GD as the test arm regimen in a future phase III trial of second-line treatment for patients with advanced STS.MethodsThe JCOG1802 study is a multicenter, selection design, randomized phase II trial comparing trabectedin (1.2 mg/m2 intravenously, every 3 weeks), eribulin (1.4 mg/m2 intravenously, days 1 and 8, every 3 weeks), and pazopanib (800 mg orally, every day) in patients with unresectable or metastatic STS refractory to doxorubicin-based first-line chemotherapy. The principal eligibility criteria are patients aged 16 years or above; unresectable and/or metastatic STS; exacerbation within 6 months prior to registration; histopathological diagnosis of STS other than Ewing sarcoma, embryonal/alveolar rhabdomyosarcoma, well-differentiated liposarcoma and myxoid liposarcoma; prior doxorubicin-based chemotherapy for STS, and Eastern Cooperative Oncology Group performance status 0 to 2. The primary endpoint is progression-free survival, and the secondary endpoints include overall survival, disease-control rate, response rate, and adverse events. The total planned sample size to correctly select the most promising regimen with a probability of > 80% is 120. Thirty-seven institutions in Japan will participate at the start of this trial.DiscussionThis is the first randomized trial to evaluate trabectedin, eribulin, and pazopanib as second-line therapies for advanced STS. We endeavor to perform a subsequent phase III trial comparing the best regimen selected by this study (JCOG1802) with GD.Trial registrationThis study was registered with the Japan Registry of Clinical Trials (jRCTs031190152) on December 5, 2019.

Trimodality Treatment of Extremity Soft Tissue Sarcoma: Where Do We Go Now?

Extremity soft tissue sarcoma (ESTS) constitutes the majority of patients with soft tissue sarcoma (STS). Patients with localized high-grade ESTS > 5cm in size carry a substantial risk of developing distant metastasis on follow-up. A neoadjuvant chemoradiotherapy approach can enhance local control by facilitating resection of the large and deep locally advanced tumors while trying to address distant spread by treating the micrometastasis for these high-risk ESTS. Preoperative chemoradiotherapy and adjuvant chemotherapy are often used for children with intermediate- or high-risk non-rhabdomyosarcoma soft tissue tumors in North America and Europe. In adults, the cumulative evidence supporting preoperative chemoradiotherapy or adjuvant chemotherapy remains controversial. However, some studies support a possible benefit of 10% in overall survival (OS) for high-risk localized ESTS, especially for those with a probability of 10-year OS < 60% using validated nomograms. Opponents of neoadjuvant chemotherapy argue that it delays curative surgery, compromises local control, and increases the rate of wound complications and treatment-related mortality; however, the published trials do not support these arguments. Most treatment-related side effects can be managed with adequate supportive care. A coordinated multidisciplinary approach involving sarcoma expertise in surgery, radiation, and chemotherapy is required to achieve better outcomes for ESTS. The next generation of clinical trials will shed light on how comprehensive molecular characterization, targeted agents and/or immunotherapy can be integrated into the upfront trimodality treatment to improve outcomes. To that end, every effort should be made to enroll these patients on clinical trials, when available.

Prostate-specific membrane antigen (PSMA) as a potential target for molecular imaging and treatment in bone and soft tissue sarcomas.

Bone and soft tissue sarcomas are a group of rare malignant tumours with major histological and anatomical varieties. In a metastatic setting, sarcomas have a poor prognosis due to limited response rates to chemotherapy. Radioligand therapy targeting prostate-specific membrane antigen (PSMA) may offer a new perspective. PSMA is a type II transmembrane glycoprotein which is present in all prostatic tissue and overexpressed in prostate cancer. Despite the name, PSMA is not prostate-specific. PSMA expression is also found in a multitude of non-prostatic diseases including a subgroup of sarcomas, mostly in its neovascular endothelial cells. On PET/CT imaging, multiple sarcomas have also shown intense PSMA-tracer accumulation. PSMA expression and PSMA-tracer uptake seem to be highest in patients with aggressive and advanced sarcomas, who are also in highest need of new therapeutic options. Although these results provide a good rationale for the future use of PSMA-targeted radioligand therapy in a selection of sarcoma patients, more research is needed to gain insight into optimal patient selection methods, PSMA-targeting antibodies and tracers, administered doses of radioligand therapy, and their efficacy and tolerability. In this review, mRNA expression of the FOLH1 gene which encodes PSMA, PSMA immunohistochemistry, PSMA-targeted imaging and PSMA-targeted therapy in sarcomas will be discussed.

Mechanical High-Intensity Focused Ultrasound (Histotripsy) in Dogs With Spontaneously Occurring Soft Tissue Sarcomas.

Histotripsy is a non-invasive focused ultrasound therapy that uses controlled acoustic cavitation to mechanically disintegrate tissue. To date, there are no reports investigating histotripsy for the treatment of soft tissue sarcoma (STS). This study aimed to investigate the in vivo feasibility of ablating STS with histotripsy and to characterize the impact of partial histotripsy ablation on the acute immunologic response in canine patients with spontaneous STS. A custom 500 kHz histotripsy system was used to treat ten dogs with naturally occurring STS. Four to six days after histotripsy, tumors were surgically resected. Safety was determined by monitoring vital signs during treatment and post-treatment physical examinations, routine lab work, and owners' reports. Ablation was characterized using radiologic and histopathologic analyses. Systemic immunological impact was evaluated by measuring changes in cytokine concentrations, and tumor microenvironment changes were evaluated by characterizing changes in infiltration with tumor-associated macrophages (TAMs) and tumor-infiltrating lymphocytes (TILs) using multiplex immunohistochemistry and differential gene expression. Results showed histotripsy ablation was achievable and well-tolerated in all ten dogs. Immunological results showed histotripsy induced pro-inflammatory changes in the tumor microenvironment. Conclusion & Significance: Overall, this study demonstrates histotripsy's potential as a precise, non-invasive treatment for STS.

Ablative Techniques for Sarcoma Metastatic Disease: Current Role and Clinical Applications.

Sarcomas are heterogenous mesenchymal neoplasms with more than 80 different histologic subtypes. Lung followed by liver and bone are the most common sites of sarcoma metastatic disease. Ablative techniques have been recently added as an additional alternative curative or palliative therapeutic tool in sarcoma metastatic disease. When compared to surgery, ablative techniques are less invasive therapies which can be performed even in non-surgical candidates and are related to decreased recovery time as well as preservation of the treated organ's long-term function. Literature data upon ablative techniques for sarcoma metastatic disease are quite heterogeneous and variable regarding the size and the number of the treated lesions and the different histologic subtypes of the original soft tissue or bone sarcoma. The present study focuses upon the current role of minimal invasive thermal ablative techniques for the management of metastatic sarcoma disease. The purpose of this review is to present the current minimally invasive ablative techniques in the treatment of metastatic soft tissue and bone sarcoma, including local control and survival rates.

Non-invasive Monitoring of Soft-tissue Sarcoma Response to Neoadjuvant Radiotherapy by Quantification of Circulating Tumor DNA (ctDNA) and Multiparametric MRI (mpMRI)

Introduction: Soft-tissue sarcomas (STS) are a heterogenous group of rare, yet malignant tumors. Wide resection remains the cornerstone of treatment for localized STS. Current S3 guidelines recommend neoadjuvant radiotherapy for primary, high-grade tumors; however, therapy response for different histological subtypes and gradings has not been systematically investigated. This ongoing prospective study evaluates the response of various STS during the course of neoadjuvant radiotherapy using innovative, non-invasive methods. Through quantification of ctDNA, tumor activity and thus therapy response will be evaluated in correlation with imaging data. Materials and Methods: Liquid biopsies: Detection of circulating tumor DNA (ctDNA) in patient blood samples through targeted next-generation sequencing (NGS). Patient-specific exome sequencing allows the detection of individual structural variants (SVs) and point mutations. Circulating free DNA (cfDNA) is isolated from peritherapeutically collected patient plasma samples and ctDNA quantified therein. Bioinformatic analysis is performed using the MIRACUM Pipeline. Multiparametric MRI (mpMRI): Combination of conventional MRI sequences with diffusion-weighted imaging (DWI) and dynamic contrast enhancement (DCE). Multiparametric MRI is performed before, during, and after neoadjuvant radiotherapy. Accurate co-registration and correlation of mpMRI with the macroscopic, histologic, and immunohistochemical resected specimen allow an analysis of morphological changes during therapy. Results: Quantification of ctDNA mirrors the clinical course and tumor activity. Furthermore, we present imaging markers that allow the characterization of tumor masses for heterogenous STS and the evaluation of therapy response. Conclusion: Liquid biopsies can be used to detect the primary tumor and metastases, and to monitor the course of therapy. Quantification of ctDNA in combination with tumor mass characterization through co-registration of mpMRI and histopathology enables the evaluation of STS response to neoadjuvant radiotherapy. The participation and support of a wider group of oncologic surgeons are needed to validate these findings on a larger patient cohort to create future tumor- and patient-specific therapy concepts.

Asymmetric Mesoporous Nanoformulation for Combination Treatment of Soft Tissue Sarcoma

Soft tissue sarcoma (STS) is a kind of tumor that is difficult to treat by chemotherapy alone. In recent years, various studies have been conducted on the use of multifunctional nanoparticles with core@shell or indiscriminate coassembly to improve therapeutic efficacy. However, in these multifunctional nanoformulations, the functional subunits are located in the relevant space, in which the different functions are difficult to perform independently during the combination therapy. Herein, the enwinding-structured asymmetric mesoporous Fe3O4&mSiO2–SRF nanoformulation (SRF = Sorafenib) is constructed for the combination therapy of STS, in which the one-dimensional mSiO2 nanorods are enwound on the surface of magnetic Fe3O4 nanoparticles. In this enwinding-structured asymmetric nanoformulation, a Fe3O4 nanosphere subunit is used for the chemodynamic therapy (CDT), and a mesoporous SiO2 (mSiO2) subunit with high surface area is used for the loading of SRF chemotherapy drugs (mSiO2–SRF). Taking advantage of the spatial isolation of mSiO2–SRF and Fe3O4 subunits, the direct exposure of the Fe3O4 subunit can not only enhance the Fenton reaction on the nanoparticles surface but also accelerate the release of Fe2+/Fe3+ in the acidic microenvironment of the tumor, which further induced the upgrade of the cell oxidation level through GSH consumption and CDT. In addition, the SRF loaded mSiO2 functional unit can inhibit the synthesis of GSH, and synergistically work with the Fe3O4 functional unit to enhance the ferroptosis of cancer cells. Compared with traditional core@shell structured nanoformulation, the cancer cell killing efficiency of the asymmetric mesoporous nanoformulation is greatly increased by 41.33%, thus realizing improved tumor restrain efficiency in STS treatment.

Brachytherapy in the Treatment of Soft-Tissue Sarcomas of the Extremities-A Current Concept and Systematic Review of the Literature.

Evidence on the use of brachytherapy in soft-tissue sarcoma (STS) is sparse. Therapy regimens are determined more by local interdisciplinary tumor conferences than by standardized protocols. Patient-specific factors complicate the standardized application of therapy protocols. The individuality of the treatment makes it difficult to compare results. A comprehensive literature search was conducted, whereby the literature from a period of almost 44 years (1977-2021) was graded and included in this systematic review. For this purpose, PubMed was used as the primary database. Search string included "soft-tissue sarcoma", "brachytherapy", and "extremity." Four independent researchers reviewed the literature. Only full-text articles written in English or German were included. Of the 175 identified studies, 70 were eligible for analysis based on the inclusion and exclusion criteria. The key points to compare were local complications, recurrence rate and correlation with margins of resection, and the use of brachytherapy regarding tumor grading. Brachytherapy represents an important subset of radiotherapy techniques used in STSs, whose indications and applications are constantly evolving, and for which a local control rate of 50% to 96% has been reported as monotherapy, depending on risk factors. However, the best benefit is seen in the combination of further resection and brachytherapy, and most authors at many other centers agree with this treatment strategy.

SAINT: A Phase I/Expanded Phase II Study Using Safe Amounts of Ipilimumab, Nivolumab and Trabectedin as First-Line Treatment of Advanced Soft Tissue Sarcoma.

This Phase 1/2 study is based on the hypothesis that immune checkpoint inhibitors are more effective when given earlier in the course of the disease for advanced soft tissue sarcoma. Phase I endpoints-maximum tolerated dose in previously treated patients; Phase II endpoints-best response, progression free survival and overall survival and incidence of adverse events in previously untreated patients; Phase I treatments-escalating doses of trabectedin (1.0, 1.2, 1.5 mg/m2) as continuous intravenous infusion over 24 h every 3 weeks, 1 mg/kg of ipilimumab given intravenously every 12 weeks, and 3 mg/kg of nivolumab given intravenously every 2 weeks; Phase II treatments-maximum tolerated dose of trabectedin and defined doses of ipilimumab and nivolumab. Phase I (n = 9)-the maximum tolerated dose of trabectedin was 1.2 mg/m2; Phase II (n = 79)-6 complete responses, 14 partial responses, 49 stable disease, 25.3% best response rate, 87.3% disease control rate; median progression-free survival, 6.7 months (CI 95%: 4.4-7.9), median overall survival, 24.6 months (CI 95%: 17.0-.); Grade 3/4 therapy-related adverse events (n = 92)-increased ALT (25%), fatigue (8.7%), increased AST (8.7%), decreased neutrophil count (5.4%) and anemia (4.6%). SAINT is a safe and effective first-line treatment for advanced soft tissue sarcoma.

Interdisciplinary Surgical Therapy of Extremity Soft-Tissue Sarcomas: A Personalized Resection and Reconstruction Algorithm.

Soft-tissue sarcomas (STS) are rare, but potentially life-threatening malignancies. STS can occur anywhere in the human body with the limbs being the most common site. Referral to a specialized sarcoma center is crucial to guarantee prompt and appropriate treatment. STS treatment strategies should be discussed in an interdisciplinary tumor board to involve expertise from all available resources, including an experienced reconstructive surgeon for an optimal outcome. In many cases, extensive resection is needed to achieve R0 resection, resulting in large defects after surgery. Hence, an evaluation of whether plastic reconstruction might be required is mandatory to avoid complications due to insufficient primary wound closure. In this retrospective observational study, we present data of patients with extremity STS treated at the Sarcoma Center, University Hospital Erlangen, in 2021. We found that complications were more frequent in patients who received secondary flap reconstruction after insufficient primary wound closure compared to patients who received primary flap reconstruction. Additionally, we propose an algorithm for an interdisciplinary surgical therapy of soft-tissue sarcomas regarding resection and reconstruction and present two problematic cases to emphasize the complexity of surgical sarcoma therapy.

MicroRNAs in the Pathogenesis, Prognostication and Prediction of Treatment Resistance in Soft Tissue Sarcomas.

Soft tissue sarcomas are highly aggressive malignant neoplasms of mesenchymal origin, accounting for less than 1% of adult cancers, but comprising over 20% of paediatric solid tumours. In locally advanced, unresectable, or metastatic disease, outcomes from even the first line of systemic treatment are invariably poor. MicroRNAs (miRNAs), which are short non-coding RNA molecules, target and modulate multiple dysregulated target genes and/or signalling pathways within cancer cells. Accordingly, miRNAs demonstrate great promise for their utility in diagnosing, prognosticating and improving treatment for soft tissue sarcomas. This review aims to provide an updated discussion on the known roles of specific miRNAs in the pathogenesis of sarcomas, and their potential use in prognosticating outcomes and prediction of therapeutic resistance.

Strategies for the Treatment of Infantile Soft Tissue Sarcomas With BCOR Alterations.

BCOR alterations are described in ultra-rare infantile soft tissue sarcomas including primitive myxoid mesenchymal tumor of infancy and undifferentiated round cell sarcoma (URCS). Previous reports often describe dismal outcomes. Thus, we undertook a retrospective, multi-institutional study of infants with BCOR -rearranged soft tissue sarcomas. Nine patients aged 6 weeks to 15 months were identified. One tumor carried a BCOR :: CCNB3 fusion, whereas 7 tumors harbored internal tandem duplication of BCOR , including 4 cases classified as primitive myxoid mesenchymal tumor of infancy, 1 case as URCS, and 2 cases characterized by a "hybrid morphology" in our evaluation. Four patients underwent upfront surgery with residual disease that progressed locally after a median of 2.5 months. Locoregional recurrences were observed in hybrid patients, and the URCS case recurred with brain metastases. Complete radiographic responses after chemotherapy were achieved in patients treated with vincristine/doxorubicin/cyclophosphamide alternating with ifosfamide/etoposide, vincristine/doxorubicin/cyclophosphamide alternating with cyclophosphamide/etoposide (regimen I), and ifosfamide/carboplatin/etoposide. Seven patients received radiotherapy. With a median of 23.5 months off therapy, 8 patients are with no evidence of disease. In our study, observation was inadequate for the management of untreated postsurgical residual disease. Tumors demonstrated chemosensitivity with anthracycline-based regimens and ifosfamide/carboplatin/etoposide. Radiotherapy was required to achieve durable response in most patients.

Comparing Ultra-hypofractionated Proton versus Photon Therapy in Extremity Soft Tissue Sarcoma.

Recent single institution, phase II evidence has demonstrated the feasibility and efficacy of ultra-hypofractionated, preoperative photon therapy in 5 fractions for the treatment of soft tissue sarcoma (STS). Our purpose was to evaluate the dosimetric benefits of modern scanning beam proton therapy compared with conventional photon radiation therapy (RT) for the neoadjuvant treatment of adult extremity STS. Existing proton and photon plans for 11 adult patients with STS of the lower extremities previously treated preoperatively with neoadjuvant RT at our center were used to create proton therapy plans using Raystation Treatment Planning System v10.A. Volumes were delineated, and doses reported consistent with International Commission on Radiation Units and Measurements reports 50, 62, and 78. Target volumes were optimized such that 100% clinical target volume (CTV) was covered by 99% of the prescription dose. The prescribed dose was 30 Gy for PT and RT delivered in 5 fractions. For proton therapy, doses are reported in GyRBE = 1.1 Gy. The constraints for adjacent organs at risk (OARs) within 1 cm of the CTV were the following: femur V30Gy ≤ 50%, joint V30Gy < 50%, femoral head V30Gy ≤ 5 cm3, strip V12 ≤ 10%, and skin V12 < 50%. Target coverage goals, OAR constraints, and integral dose were compared by Student t test with P < .05 significance. A minimum 99% CTV coverage was achieved for all plans. OAR dose constraints were achieved for all proton and photon plans; however, mean doses to the femur (10.7 ± 8.5 vs 16.1 ± 7.7 GyRBE), femoral head (2.0 ± 4.4 vs 3.6 ± 6.4 GyRBE), and proximal joint (1.8 ± 2.4 vs 3.5 ± 4.4 GyRBE) were all significantly lower with PT vs intensity-modulated radiation therapy (IMRT) (all P < .05). Integral dose was significantly reduced for proton vs photon plans. Conformity and heterogeneity indices were significantly better for proton therapy. Proton therapy maintained target coverage while significantly reducing integral and mean doses to the proximal organs at risk compared with RT. Further prospective investigation is warranted to validate these findings and potential benefit in the management of adult STS.

Pazopanib Treatment in Soft Tissue Sarcoma (Single Center Experience)

Pazopanib Treatment in Soft Tissue Sarcoma (Single Center Experience)