Treatment Of Soft Tissue Sarcomas Research Articles

Integrative analysis of TROAP with molecular features, carcinogenesis, and related immune and pharmacogenomic characteristics in soft tissue sarcoma.

Soft tissue sarcoma (STS) is an uncommon malignancy that often carries a grim prognosis. Trophinin-associated protein (TROAP) is augmented in a variety of tumors and can affect tumor proliferation. Nevertheless, the prognostic value and specific functions of TROAP in STS are still vague. Herein, we display that TROAP exhibits an augmented trend in STS, and its elevation correlates with a poor prognosis of STS. Furthermore, its reduction is related to increased immune cell infiltration, enhanced stroma, and elevation of immune activation. Meanwhile, the TROAP-derived genomic signature is validated to predict patient prognosis, immunotherapy, and drug response reliably. A nomogram constructed based on age, metastatic status, and a TROAP-derived risk score of an STS individual could be used to quantify the survival probability of STS. In addition, in vitro experiments have demonstrated that TROAP is overexpressed in STS, and the downregulation of TROAP could affect the proliferation, migration, metastasis, and cell cycle of STS cells. In summary, the TROAP expression is elevated in STS tissues and cells, which is related to the poor prognosis and malignant biological behaviors of STS. It could act as a potential prognostic biomarker for diagnosis and treatment of STS.

Follow-Up after Curative Surgical Treatment of Soft-Tissue Sarcoma for Early Detection of Recurrence: Which Patients Have More or Fewer Visits than Advised in Guidelines?

Follow-up (FU) in soft-tissue sarcoma (STS) patients is designed for early detection of disease recurrence. Current guidelines are not evidenced-based and not tailored to patient or tumor characteristics, so they remain debated, particularly given concerns about cost, radiation frequency, and over-testing. This study assesses the extent to which STS patients received guideline-concordant FU and to characterize which type of patients received more or fewer visits than advised. All STS patients surgically treated at the Leiden University Medical Center between 2000-2020 were included. For each patient, along with individual characteristics, all radiological examinations from FU start up to 5 years were included and compared to guidelines. Recurrence was defined as local/regional recurrence or metastasis. A total of 394 patients was included, of whom 250 patients had a high-grade tumor (63.5%). Only 24% of patients received the advised three FU visits in the first year. More FU visits were observed in younger patients and those diagnosed with a high-grade tumor. Among patients with a recurrence, 10% received fewer visits than advised, while 28% of patients without a recurrence received more visits than advised. A minority of STS patients received guideline-concordant FU visits, suggesting that clinicians seem to incorporate recurrence risk in decisions on FU frequency.

Femoro-popliteal autogenous venous bypass in surgical treatment of soft tissue sarcomas of the lower limbs: clinical case

Femoro-popliteal autogenous venous bypass in surgical treatment of soft tissue sarcomas of the lower limbs: clinical case

Argon-helium knife cryoablation plus programmed cell death protein 1 inhibitor in the treatment of advanced soft tissue sarcomas: there is no evidence of the synergistic effects of this combination therapy.

Effective treatment for advanced soft tissue sarcomas (STSs) is necessary for improved outcomes. Previous studies have suggested that cryoablation can have a synergistic effect with programmed cell death protein-1 (PD-1) inhibitor in the treatment of malignancy. This study aimed to clarify the efficacy and safety of argon-helium knife cryoablation in combination with PD-1 inhibitor in the treatment of STSs. Retrospectively collected and analyzed the clinical data of patients with advanced STS who underwent cryoablation and PD-1 inhibitor between March 2018 and December 2021. This study included 27 patients with advanced STS. In terms of target lesions treated with cryoablation, 1 patient achieved complete response, 15 patients had partial response (PR), 10 patients had stable disease, and 1 patient had progressive disease. This corresponded to an overall response rate of 59.3% and a disease control rate of 96.3%. In terms of distant target lesions untreated with cryoablation, only two patients had a PR compared to the diameter of the lesion before ablation. The combination therapy was relatively well tolerated. None of the patients experienced treatment-related death or delayed treatment due to adverse events. Cryoablation combined with PD-1 inhibitors in the therapy of advanced STS is safe and can effectively shrink the cryoablation-target lesion. However, there is no evidence of the synergistic effects of this combination therapy.

Chemoradiotherapy plus hyperthermia (CRTH) versus chemoradiotherapy (CRT) alone in neoadjuvant treatment of soft tissue sarcoma: tumor response, treatment toxicity and disease control

Introduction Neoadjuvant chemotherapy and radiotherapy for the management of soft tissue sarcomas (STS) are still preferably delivered sequentially, with or without concurrent hyperthermia. Concurrent delivery of chemo-, radio- and thermotherapy may produce synergistic effects and reduce chemotherapy-free intervals. The few available studies suggest that concurrent chemoradiation (CRT) has a greater local effect. Data on the efficacy and toxicity of adding hyperthermia to CRT (CRTH) are sparse. Materials and methods A cohort of 101 patients with STS of the extremities and trunk who received CRT (n = 33) or CRTH (n = 68) before resection of macroscopic tumor (CRT: n = 19, CRTH: n = 49) or re-resection following a non-oncological resection, so called ‘whoops procedure’, (CRT: n = 14, CRTH: n = 19) were included in this retrospective study. CRT consisted of two cycles of doxorubicine (50 mg/m2 on d2) plus ifosfamide (1500 mg/m2 on d1-5, q28) plus radiation doses of up to 60 Gy. Hyperthermia was delivered in two sessions per week. Results All patients received the minimum dose of 50 Gy. Median doses of ifosfamide and doxorubicin were comparable between CRT (75%/95%) and CRTH (78%/97%). The median number of hyperthermia sessions was seven. There were no differences in acute toxicities. Major wound complications occurred in 15% (CRT) vs. 25% (CRTH) (p = 0.19). In patients with macroscopic disease, the addition of hyperthermia resulted in a tendency toward improved remission: regression ≥90% occurred in 21/48 (CRTH) vs. 4/18 (CRT) patients (p = 0.197). With a median postoperative follow-up of 72 months, 6-year local control and overall survival rates for CRTH vs. CRT alone were 85 vs. 78% (p = 0.938) and 79 vs. 71% (p = 0.215). Conclusions Both CRT and CRTH are well tolerated with an expected rate of wound complications. The results suggest that adding hyperthermia may improve tumor response.

Chemotherapeutic drugs for soft tissue sarcomas: a review.

Despite the low incidence of soft tissue sarcomas (STSs), hundreds of thousands of new STS cases are diagnosed annually worldwide, and approximately half of them eventually progress to advanced stages. Currently, chemotherapy is the first-line treatment for advanced STSs. There are difficulties in selecting appropriate drugs for multiline chemotherapy, or for combination treatment of different STS histological subtypes. In this study, we first comprehensively reviewed the efficacy of various chemotherapeutic drugs in the treatment of STSs, and then described the current status of sensitive drugs for different STS subtypes. anthracyclines are the most important systemic treatment for advanced STSs. Ifosfamide, trabectedin, gemcitabine, taxanes, dacarbazine, and eribulin exhibit certain activities in STSs. Vinca alkaloid agents (vindesine, vinblastine, vinorelbine, vincristine) have important therapeutic effects in specific STS subtypes, such as rhabdomyosarcoma and Ewing sarcoma family tumors, whereas their activity in other subtypes is weak. Other chemotherapeutic drugs (methotrexate, cisplatin, etoposide, pemetrexed) have weak efficacy in STSs and are rarely used. It is necessary to select specific second- or above-line chemotherapeutic drugs depending on the histological subtype. This review aims to provide a reference for the selection of chemotherapeutic drugs for multi-line therapy for patients with advanced STSs who have an increasingly long survival.

Preparation of pazopanib-fumarate disodium glycyrrhizinate nanocrystalline micelles by liquid-assisted ball milling

Pazopanib (PZ) is a multikinase inhibitor, which is mainly used in the treatment of soft tissue sarcoma and advanced renal cancer. However, because of its water insolubility, oral bioavailability is poor. At the same time, photo lability and high dose oral administration lead to severe hepatotoxicity, which is limited in clinical application. In this paper, the novel pazopanib-fumarate disodium glycyrrhizinate nanocrystalline micelles are successfully prepared by liquid-assisted ball milling. The prepared cocrystals and nanocrystalline micelle structures are systematically characterized by X-ray diffraction (XRD), differential scanning calorimetry (DSC) and Fourier Transform Infrared Spectrometer (FTIR) analysis. In vitro solubility and dissolution experiments show that the solubility and dissolution of nanocrystalline micelles are significantly improved under different simulated physiological conditions. The accelerated stabilization experiments show that the nanocrystalline micelles have good physical and chemical stability and showed excellent stability in water (Zeta potential was 62.39 mV). In addition, the in vivo bioavailability of nanocrystalline micelles is 3 times higher than that of PZ, and the therapeutic threshold (> 20 μg/mL) is up to 30 h. This new strategy provides a feasible solution to the undesirable properties of PZ.

The current management of clear cell sarcoma.

Clear cell sarcoma (CCS) is a rare melanocytic soft tissue sarcoma with a high propensity for lymphatic metastasis and poor prognosis. It is characterized by the translocation of t (12;22), resulting in the rearrangement of the EWSR1 gene and overexpression of MET. Despite improvements in the diagnosis and treatment of soft tissue sarcomas, the management of CCSs remains challenging owing to their rarity, unique biological behaviour and limited understanding of their molecular pathogenesis. The standard treatment for localized CCSs is surgical excision with negative margins. However, there is an ongoing debate regarding the role of adjuvant chemotherapy, radiotherapy and lymphadenectomy in the management of this disease. CCSs are usually resistant to conventional chemotherapy. Targeted therapies, such as sunitinib and MET inhibitors, may provide promising results. Immunotherapy, particularly immune checkpoint inhibitors, is currently under investigation as a potential treatment option for CCSs. Further research is needed to better understand the biology of CCSs and develop effective therapeutic strategies. The purpose of this review is to provide a comprehensive overview of current knowledge and advances in the diagnosis and treatment of CCSs.

Integration analysis of senescence-related genes to predict prognosis and immunotherapy response in soft-tissue sarcoma: evidence based on machine learning and experiments.

Background: Soft tissue sarcoma (STS) is the malignancy that exhibits remarkable histologic diversity. The diagnosis and treatment of STS is currently challenging, resulting in a high lethality. Chronic inflammation has also been identified as a key characteristic of tumors, including sarcomas. Although senescence plays an important role in the progression of various tumors, its molecular profile remains unclear in STS. Methods: We identified the senescence-related genes (SRGs) in database and depicted characteristics of genomic and transcriptomic profiling using cohort within TCGA and GEO database. In order to investigate the expression of SRGs in different cellular subtypes, single-cell RNA sequencing data was applied. The qPCR and our own sequencing data were utilized for further validation. We used unsupervised consensus clustering analysis to establish senescence-related clusters and subtypes. A senescence scoring system was established by using principal component analysis (PCA). The evaluation of clinical and molecular characteristics was conducted among distinct groups. Results: These SRGs showed differences in SCNV, mutation and mRNA expression in STS tissues compared to normal tissues. Across several cancer types, certain shared features of SRGs were identified. Several SRGs closely correlated with immune cell infiltration. Four clusters related to senescence and three subtypes related to senescence, each with unique clinical and biological traits, were established. The senescence scoring system exhibited effectiveness in predicting outcomes, clinical traits, infiltrations of immune cells and immunotherapy responses. Conclusion: Overall, the current study provided a comprehensive review of molecular profiling for SRGs in STS. The SRGs based clustering and scoring model could help guiding the clinical management of STS.

Safe and effective use of cabozantinib and nivolumab in stabilizing disease progression of tissue sarcoma after multiple lines of standard therapy

Introduction: Soft-tissue sarcomas (STS) are a rare and varied group of tumors with limited treatment options. In recent years, immune checkpoint inhibitors have demonstrated efficacy in an increasing number of solid tumors. Nivolumab, a PD1-inhibitor, demonstrates improved overall survival (OS) and progression-free survival (PFS) in renal cell carcinoma, melanoma, and gastrointestinal stromal tumor (GIST). The tyrosine kinase inhibitor (TKI), cabozantinib, demonstrates an antitumor effect in osteosarcoma and Ewing sarcoma. Case Series: Here we describe two patients with recurrent and refractory STS. Both patients failed multiple lines of conventional therapy including neoadjuvant radiation, surgical resection, and palliative chemotherapy before achieving partial response with combination cabozantinib and nivolumab. Conclusion: These cases demonstrate the safety and efficacy of using combination nivolumab and cabozantinib in treatment of STS warranting further investigation of immunotherapy treatment.

Characterization of a rhabdomyosarcoma reveals a critical role for SMG7 in cancer cell viability and tumor growth

Soft-tissue sarcomas (STSs) are a rare and diverse group of mesenchymal cancers plagued with aggression, poor response to systemic therapy, and high rates of recurrence. Although STSs generally have low mutational burdens, the most commonly mutated genes are tumor suppressors, which frequently acquire mutations inducing nonsense-mediated mRNA decay (NMD). This suggests that STS cells may exploit NMD to suppress these anti-cancer genes. To examine the role that the NMD factor SMG7 plays in STS, we developed an inducible knockout mouse model in the Trp53−/− background. Here, we isolated a subcutaneous STS and identified it as a rhabdomyosarcoma (RMS). We report that knockout of SMG7 significantly inhibited NMD in our RMS cells, which led to the induction of NMD targets GADD45b and the tumor suppressor GAS5. The loss of NMD and upregulation of these anti-cancer genes were concomitant with the loss of RMS cell viability and inhibited tumor growth. Importantly, SMG7 was dispensable for homeostasis in our mouse embryonic fibroblasts and adult mice. Overall, our data show that the loss of SMG7 induces a strong anti-cancer effect both in vitro and in vivo. We present here the first evidence that disrupting SMG7 function may be tolerable and provide a therapeutic benefit for STS treatment.

Efficacy of second and third lines of treatment in advanced soft tissue sarcomas: a real-world study.

Soft tissue sarcomas (STSs) are an uncommon and heterogeneous group of tumours. Several drugs and combinations have been used in clinical practice as second-line (2L) and third-line (3L) treatment. The growth modulation index (GMI) has previously been used as an exploratory efficacy endpoint of drug activity and represents an intra-patient comparison. We performed a real-world retrospective study including all patients with advanced STS who had received at least 2 different lines of treatment for advanced disease between 2010 and 2020 at a single institution. The objective was to study the efficacy of both 2L and 3L treatments, analysing the time to progression (TTP) and the GMI (defined as the ratio of TTP between 2 consecutive lines of therapy). Eighty-one patients were included. The median TTP after 2L and 3L treatment was 3.16 and 3.06months, and the median GMI was 0.81 and 0.74, respectively. The regimens most frequently used in both treatments were trabectedin, gemcitabine-dacarbazine, gemcitabine-docetaxel, pazopanib and ifosfamide. The median TTP by each of these regimens was 2.80, 2.23, 2.83, 4.10, and 5.00months, and the median GMI was 0.78, 0.73, 0.67, 1.08, and 0.94, respectively. In terms of histotype, we highlight the activity (GMI > 1.33) of gemcitabine-dacarbazine in undifferentiated pleomorphic sarcoma (UPS) and in leiomyosarcoma, pazopanib in UPS, and ifosfamide in synovial sarcoma. In our cohort, regimens commonly used after first-line STS treatment showed only slight differences in efficacy, although we found significant activity of specific regimens by histotype.

Isolated Limb Infusion for Limb-Threatening, Unresectable Sarcoma: Past Progress, Current Applications, and Future Directions.

Treatment of soft tissue sarcomas (STSs) is complicated by disease heterogeneity. Further, it has not benefitted much from the recent therapeutic advances in other soft tissue malignancies. Surgical resection remains the gold standard in resectable disease, but unresectable, locally advanced STS requires alternative and multimodal approaches. Isolated limb infusion (ILI) provides regional chemotherapy to extremity STS and offers the potential for limb salvage. Despite being in use for nearly 3 decades, there is limited literature on ILI in STS. This review provides an overview of patient eligibility, the procedure, significant publications in this field, and opportunities for further progress.

Integrative profiling analysis reveals prognostic significance, molecular characteristics, and tumor immunity of angiogenesis-related genes in soft tissue sarcoma.

Soft tissue sarcoma (STS) is a class of malignant tumors originating from mesenchymal stroma with a poor prognosis. Accumulating evidence has proved that angiogenesis is an essential hallmark of tumors. Nevertheless, there is a paucity of comprehensive research exploring the association of angiogenesis-related genes (ARGs) with STS. The ARGs were extracted from previous literature, and the differentially expressed ARGs were screened for subsequent analysis. Next, the least absolute shrinkage and selection operator (LASSO) and Cox regression analyses were conducted to establish the angiogenesis-related signature (ARSig). The predictive performance of the novel ARSig was confirmed using internal and external validation, subgroup survival, and independent analysis. Additionally, the association of the ARSig with the tumor immune microenvironment, tumor mutational burden (TMB), and therapeutic response in STS were further investigated. Notably, we finally conducted in vitro experiments to verify the findings from the bioinformatics analysis. A novel ARSig is successfully constructed and validated. The STS with a lower ARSig risk score in the training cohort has an improved prognosis. Also, consistent results were observed in the internal and external cohorts. The receiver operating characteristic (ROC) curve, subgroup survival, and independent analysis further indicate that the novel ARSig is a promising independent prognostic predictor for STS. Furthermore, it is proved that the novel ARSig is relevant to the immune landscape, TMB, immunotherapy, and chemotherapy sensitivity in STS. Encouragingly, we also validate that the signature ARGs are significantly dysregulated in STS, and ARDB2 and SRPK1 are closely connected with the malignant progress of STS cells. In sum, we construct a novel ARSig for STS, which could act as a promising prognostic factor for STS and give a strategy for future clinical decisions, immune landscape, and personalized treatment of STS.

Randomized phase II trial of cabozantinib combined with PD-1 and CTLA-4 inhibition versus cabozantinib in metastatic soft tissue sarcoma.

LBA11504 Background: Cabozantinib (C) has been combined successfully with either PD-1 or CTLA-4 inhibition in cancer clinical trials. The combination of nivolumab (N) and ipilimumab (I) previously was evaluated in soft tissue sarcoma (STS) and demonstrated activity as well as an acceptable safety profile. Given these data, we hypothesize that C in combination with both I and N is a therapeutic strategy that will be more effective than C alone in metastatic STS that lack translocations. Additionally, we hypothesized that C priming would enhance the efficacy of combination I and N at the time of crossover. Methods: This is a 2:1 randomized phase 2 clinical trial evaluating the overall response rate (RR) of C 40mg orally daily in combination with I (1mg/kg IV) / N (3mg/kg) for 4 doses Q3W and then maintenance N 480mg Q4W compared to C 60mg oral alone, with crossover. Secondary endpoints include progression free survival (PFS), disease control rate (DCR), RR in crossover, quality of life by FACT-G7, RR by iRECIST and safety. Correlative and biomarker analysis are preplanned. Key patient selection includes ECOG 0-1, 1-2 lines of prior therapy, and sarcomas that lack of translocations. The trial was balanced for leiomyosarcoma (LMS), liposarcoma and UPS. Results: 69 patients were randomized to C+I/N and 36 patients were randomized to C alone. 19 patients crossed over to C+I/N at progression. 54/105 patients had LMS. RR of C+I/N was 11% (5 PR and 2 CR), while the RR of C was 6% (2 PR and 0 CR) (p = NS). C+I/N responding histologies included LMS, angiosarcoma, epithelioid sarcoma, and myxofibrosarcoma. C responding histologies included 2 PRs in LMS. There were also 2 LMS PRs in crossover to C+I/N. The median PFS for C+I/N was 5.4 months and for C was 3.8 months (p = 0.016). The DCR for C+I/N was 80% (41 SD, 5 PR, 2 CR), and 42% for C (11 SD, 2 PR) (p = 0.0004). The most common grade 3-4 adverse events affecting > 10% of patients included hypothyroidism, diarrhea, mucositis, oral dysesthesia, nausea, vomiting, elevated AST and ALT, anorexia, dysgeusia, headache, pruritis, maculopapular rash, and hypertension for C+I/N and hypothyroidism, diarrhea, oral dysesthesia, fatigue, palmar-plantar erythrodysesthesia, and hypertension for C. Conclusions: The combination of C+I/N was superior to C for the treatment of non-translocation STS for DCR and PFS. Most frequent responding histology was LMS. Correlative work is ongoing. Clinical trial information: NCT04551430 .

A Case Report on Brachytherapy in Extremity Soft Tissue Sarcoma (STS)

STS represents a heterogenous group of malignancies with varying pathological grades, sites of origin and histologies. In the olden days, treatment consisted of resections and amputation which led to significant detriment in quality of life(QoL) and structural functions . Here we present a case of 49 year old patients who came with complaints of painless, progressive swelling in the right upper arm. He underwent WLE followed by intraoperative brachytherapy catheter application. He was then planned for HDR brachytherapy 34 Gy in 10 fractions 4 days following surgery. He tolerated the treatment well, the surgical scar healed by primary intention with no complication during or after the procedure. It can be concluded that brachytherapy in soft tissue sarcoma is a feasible option and an effective modality in the treatment of extremity soft tissue sarcoma with adequate local control.

Moderate hypofractionated radiation therapy and pathologic response for soft tissue sarcomas (STS) of limbs and trunk: experience from a tertiary cancer center.

Preoperative radiation therapy following by limb-sparing or conservative surgery is a standard approach for limb and trunk STS. Data supporting hypofractionated radiotherapy schedules are scarce albeit biological sensitivity of STS to radiation would justify it. We sought to evaluate the impact of moderate hypofractionation on pathologic response and its influence on oncologic outcomes. From October 2018 to January 2023, 18 patients with limb or trunk STS underwent preoperative radiotherapy at a median dose of 52.5Gy (range 49.5-60Gy) in 15 fractions of 3.5Gy (3.3-4Gy) with or without neoadjuvant chemotherapy. A favorable pathologic response (fPR) was considered as ≥ 90% tumor necrosis on specimen examination. All patients completed planned preoperative radiotherapy. Eleven patients (61.1%) achieved a fPR, and 7 patients (36.8%) a complete pathologic response with total disappearance of tumor cells. Nine patients (47%) developed grade 1-2 acute skin toxicity, and 7 patients (38.8%) had wound complications on follow-up. With a median follow-up of 14months (range 1-40), no cases of local relapse were observed, and actuarial 3-year overall survival (OS) and distant metastases-free survival (DMFS) are 87% and 76.4%, respectively. In the univariate analysis, the presence of a favorable pathologic response (fPR) was associated with improved 3-year OS (100% vs. 56.03%, p = 0.058) and 3-year DMFS (86.91% vs. 31.46%, p = 0.002). Moreover, both complete or partial RECIST response and radiological stabilization of the tumor lesion showed a significant association with higher rates of 3-year distant metastasis-free survival (DMFS) (83% vs. 83% vs. 56%, p < 0.001) and 3-year overall survival (OS) (100% vs. 80% vs. 0, p = 0.002). Preoperative moderate hypofractionated radiation treatment for STS is feasible and well tolerated and associates encouraging rates of pathologic response that could have a favorable impact on final outcomes.

A phase II study of fruquintinib in the first- (1L) or second-line (2L) treatment of unresectable metastatic soft tissue sarcoma.

e23547 Background: Standard treatment for patients with unresectable metastatic soft-tissue sarcoma is chemotherapy based on anthracyclines, while the tolerance of chemotherapy is limited. We assessed if fruquintinib, a highly selective tyrosine kinase inhibitor of VEGFR-1, -2, and -3 is effective and safe in the 1L or 2L treatment for these patients. Methods: This is a single-arm, prospective, single-center clinical study. The inclusion criteria were patients with pathologically confirmed unresectable metastatic STS (including desmoplastic small round cell tumors, epithelioid hemangioendothelioma, hemangiopericytoma/malignant solitary fibroma, and chemotherapy-failed hemangiosarcoma), at least one measurable lesion (according to RECIST 1.1), with the normal function of main organs. Other inclusion criteria included ECOG PS 0-2 and anti-angiogenesis treatment naïve. Patients were administrated 5mg fruquintinib once daily for 3 weeks every 4 weeks until disease progression or unacceptable toxicity. The primary study endpoint was Progression free survival (PFS). Objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and adverse event was also calculated. Results: Data cutoff date was January 31 2023. 14 patients (9 males and 5 females) were enrolled. The median age is 50.1 (range 21-69). Pathological types included: Hemangiopericytoma/malignant solitary fibroma (n=6); Epithelioid Hemangioendothelioma (n=6) and Hemangiosarcoma (n=2). 2 patients were died, the median PFS was 8.1 m. 14 patients were eligible for the evaluation of tumor response. 3 patients (2 cases of Hemangiosarcoma and 1 case of Epithelioid Hemangioendothelioma) achieved partial response (PR) and the ORR was 21.4 %(3/14). 10 patients had stable disease (SD) and the DCR was 92.9% (13/14). Most adverse events were hypertension, fatigue, and hemorrhage. The most Grade 3/4 adverse effect is hypertension and abnormal liver function. Conclusions: The fruquintinib showed a promising efficacy and favorable tolerance in the 1L or 2L treatment of unresectable metastatic soft-tissue sarcoma. Clinical trial information: NCT05142631 .

Immunotherapy Plus Radiotherapy for the Treatment of Sarcomas: Is There a Potential for Synergism?

Soft tissue sarcoma (STS) is a highly heterogeneous malignant tumor derived from mesenchymal tissue. Advanced STS has a poor response to the current anti-cancer therapeutic options, with a median overall survival of less than two years. Thus, new and more effective treatment methods for STS are needed. Increasing evidence has shown that immunotherapy and radiotherapy have synergistic therapeutic effects against malignant tumors. In addition, immunoradiotherapy has yielded positive results in clinical trials for various cancers. In this review, we discuss the synergistic mechanism of immunoradiotherapy in cancer treatment and the application of this combined regimen for the treatment of several cancers. In addition, we summarize the existing evidence on the use of immunoradiotherapy for the treatment of STS and the relevant clinical trials that are currently ongoing. Furthermore, we identify challenges in the use of immunoradiotherapy for the treatment of sarcomas and propose methods and precautions for overcoming these challenges. Lastly, we propose clinical research strategies and future research directions to help in the research and treatment of STS.

Study of microwave ablation in patients with unresectable soft tissue sarcoma.

e23545 Background: Currently, the main treatment for soft tissue sarcoma is a combination of radiotherapy, chemotherapy and complete surgical resection. However, there is no ideal method for soft tissue sarcoma after multiple recurrences, large tumours, insensitivity to radiotherapy or failure of down grade therapy. Microwave ablation is one of the main techniques for tumour thermal therapy, but its use in soft tissue sarcoma is not yet widespread. The aim of this study was to investigate the safety and efficacy of microwave ablation in refractory soft tissue sarcoma. Methods: Fourteen eligible patients with refractory soft tissue sarcoma were treated with local anaesthesia, multi-point intra-tumour needle placement under ultrasound guidance and local radiofrequency ablation (20-40 J, 2-5 minutes). For tumours larger than 5 cm in diameter, repeat ablation can be performed after 3-4 weeks. Of the 14 patients, 8 were male and 6 were female, with a mean age of 58.91 years. There were 4 cases of myxofibrosarcoma, 3 cases of dedifferentiated liposarcoma, 2 cases of malignant nerve sheath tumour, 2 cases of clear cell sarcoma and 3 cases of other sarcomas. Tumours were located in the trunk in 7 cases, in the upper limbs in 3 cases and in the lower limbs in 4 cases. Of these, 5 patients had two operations and 9 patients had three or more operations. Four cases had received first-line therapy, five cases had received second-line therapy, and five cases had received third-line therapy or more. Postoperative pain relief and wound complications were recorded. MRI was performed regularly to assess tumour shrinkage. Results: Post-operatively, all patients experienced a significant reduction in local swelling and pain. Post-operative imaging showed partial response (PR) in 11 cases and stable disease (SD) in 3 cases. The overall response rate (ORR) was 78.57%. Progression-free survival (PFS) ranged from 2-18 months with a median of 5.82 months. Complications included tumour ulceration in 2 cases, skin burns with necrosis in 2 cases and postoperative fever in 5 cases. Conclusions: For soft tissue sarcomas that cannot be removed by surgery, where tumour growth is slow and insensitive to radio/chemotherapy, local microwave ablation can achieve tumour shrinkage and reduce patient symptoms such as local swelling and pain. It is an effective treatment option for some specific sarcoma patients.