Recurrent Soft Tissue Sarcoma Research Articles

Combined Use of the Hemi-Split Tibialis Anterior Muscle and Soleus Muscle Flap for Reconstruction After the Excision of a Recurrent Soft Tissue Sarcoma in the Lower Leg

Combined Use of the Hemi-Split Tibialis Anterior Muscle and Soleus Muscle Flap for Reconstruction After the Excision of a Recurrent Soft Tissue Sarcoma in the Lower Leg

Safety and Efficacy of Percutaneous Cryoablation for Recurrent or Metastatic Soft Tissue Sarcoma in Adult Patients.

Background: Treatment options are limited in patients with recurrent or metastatic disease after initial treatment of soft tissue sarcoma (STS) by surgical resection, radiation, or systemic therapy. Percutaneous cryoablation may provide a complementary minimally invasive option in this setting. Objective: To assess the safety and efficacy of percutaneous cryoablation performed for local control of treatment-refractory recurrent or metastatic STS. Methods: This single-institution retrospective study included adult patients who underwent percutaneous cryoablation from March 2016 to April 2023 to achieve local control of recurrent or metastatic STS after earlier treatment (surgery, radiation, or chemotherapy). For each treated lesion, a single interventional radiologist re-reviewed intraprocedural images to assess for adequate coverage by the ice ball of the entire lesion and a ≥5-mm margin in all dimensions. Complications and outcomes were extracted from medical records. The primary endpoint for procedure efficacy was 1-year local progression-free survival. Results: The study included 141 patients (median age, 66 years; 90 female, 51 male) who underwent 217 cryoablation procedures to treat 250 recurrent or metastatic STS lesions. The most common STS histologic types were leiomyosarcoma (56/141) and liposarcoma (39/141). Lesions had a mean long-axis diameter of 2.0 cm (range, 0.4-11.0 cm). Adequate ice-ball coverage was achieved for 82% (204/250) of lesions. The complication rate was 2% (4/217), entailing three major complications and one minor complication. Patients' median post-ablation follow-up was 25 months (range, 3-80 months). Local progression-free survival was 86% at 1 year and 79% at 2 years. Chemotherapy-free survival was 45% at 1 year and 31% at 2 years. Overall survival (OS) was 89% at 1 year and 80% at 2 years. In Kaplan-Meier analysis, leiomyosarcoma, in comparison with liposarcoma, had significantly higher local progression-free survival, but no significant difference in OS. In multivariable analysis, factors independently associated with an increased risk for local progression included inadequate ice-ball coverage (HR=7.73) and a lesion location of peritoneum (HR=3.63) or retroperitoneum (HR=3.71) relative to lung. Conclusion: Percutaneous cryoablation has a favorable safety and efficacy profile in patients with recurrent or metastatic STS after earlier treatments. Clinical Impact: Percutaneous cryoablation should be considered for local control of treatment-refractory STS.

Beyond Clinical Examination: Utilizing MRI Surveillance to Detect Recurrence of Soft Tissue Sarcomas and Differentiate from Posttherapeutic Changes.

Early detection of soft tissue sarcoma (STS) recurrence is essential; however, the role and timeline of Magnetic resonance imaging (MRI) surveillance are still under debate. The aim of this study was to determine whether local recurrence (LR) could be identified via clinical examination alone and to assess the MRI morphology of primary STS and LR. This retrospective study included all patients with STS recurrence after surveillance for at least five years from the tumor database of the Medical University of Vienna from 2000 until December 2023. The characteristics of primary STS and LR and the time interval to recurrence and clinical detectability were assessed. The MRIs of LR and posttherapeutic changes (PTC) were compared with the initial MRIs. A total of 57 patients (60% male; mean age 58.5 ± 18.0 years) with STS and histologically confirmed LR were included. The mean time interval to LR was 2.3 ± 1.8 years (range 108 to 3037 days). The clinically detectable recurrences were significantly larger than the inapparent ones (71.9 cm3 vs. 7.0 cm3; p < 0.01). The MRI morphology of all LRs (26/26) closely resembled the initial STS. For comparison, nine patients were included with clinically suspected LRs, which were histologically proven to be PTC. None of these resembled the primary STS. Based on clinical symptoms alone, especially small and early recurrences can be missed, which supports the importance of MRI surveillance.

Local recurrence rates of superficial versus deep soft tissue sarcoma.

Soft tissue sarcomas are a group of malignancies that commonly occur in the extremities. As deep lesions may exist within the confines of the muscular fascia, we postulate that local recurrence rates are higher for superficial soft tissue sarcomas managed by the standard of care. A retrospective review was performed on 90 patients who underwent surgical resection of soft tissue sarcomas of the extremity from 2007 to 2015. Patients with minimum 2-year follow-up and adequate operative, pathologic, and clinical outcomes data were included. Mean age was 54 ± 18 years with 49 (54.4%) patients being male. Lesions in 77.8% of cases were deep, and 22.2% were superficial to fascia. Following the index surgical resection, a total of 33 (36.7%) patients had positive margins. A total of 17 (18.9%) patients had a local recurrence. Overall, 3-year survival was 92.7%, and 5-year survival was 79.0%. Five-year recurrence-free survival of deep sarcomas was 91.1% versus 58.2% of superficial lesions (p = 0.006). Patients with higher tumor depth had lower odds of experiencing a local recurrence (HR 0.26 [95% CI 0.09-0.72]). Local recurence rates was also associated with positive surgical margins on initial resection (33.3% versus 12.3%) (p = 0.027). In this series, superficial tumor depth was associated with local recurrence of soft tissue sarcomas of the extremity following surgical resection. Positive surgical margins was also associated with local recurrence.

Durvalumab plus pazopanib combination in patients with advanced soft tissue sarcomas: a phase II trial

We aimed to determine the activity of the anti-VEGF receptor tyrosine-kinase inhibitor, pazopanib, combined with the anti-PD-L1 inhibitor, durvalumab, in metastatic and/or recurrent soft tissue sarcoma (STS). In this single-arm phase 2 trial (NCT03798106), treatment consisted of pazopanib 800 mg orally once a day and durvalumab 1500 mg once every 3 weeks. Primary outcome was overall response rate (ORR) and secondary outcomes included progression-free survival (PFS), overall survival, disease control rate, immune-related response criteria, and safety. The ORR was 30.4% and the trial met the pre-specified endpoint. The median PFS was 7.7 months (95% confidence interval: 5.7–10.4). The common treatment-related adverse events of grades 3–4 included neutropenia (9 [19.1%]), elevated aspartate aminotransferase (7 [14.9%]), alanine aminotransferase (5 [10.6%]), and thrombocytopenia (4 [8.5%]). In a prespecified transcriptomic analysis, the B lineage signature was a significant key determinant of overall response (P = 0.014). In situ analysis also showed that tumours with high CD20+ B cell infiltration and vessel density had a longer PFS (P = 6.5 × 10−4) than those with low B cell infiltration and vessel density, as well as better response (50% vs 12%, P = 0.019). CD20+ B cell infiltration was identified as the only independent predictor of PFS via multivariate analysis. Durvalumab combined with pazopanib demonstrated promising efficacy in an unselected STS cohort, with a manageable toxicity profile.

Indicators of free radical oxidation in neutrophils of patients with primary and recurrent soft tissue sarcomas

Purpose of the study. To carry out a comparative analysis of lipid peroxidation intensity and antioxidant system indices in blood neutrophils of patients with primary and relapsed soft tissue sarcomas (STS) depending on sex and age.Patients and methods. Of the 81 patients included in the study, 48 had primary STS, 5 patients with continued growth, and 28 patients with recurrent STS. The patients were divided by sex and age; the level of lipid peroxidation products, superoxide dismutase (SOD) activity, total peroxidase activity (TPA), glutathione peroxidase (GPx) activity and reduced glutathione (RG) content in blood neutrophils were investigated by conventional spectrophotometric methods. The comparison groups (donors) consisted of 12 men and 17 women divided into the same age subgroups: ≤ 45 years and &gt; 45 years.Results. In donors, there was a multiple decrease in the SOD/TPA ratio with age, especially in women, and in men this was accompanied by an age-related decrease in GPx activity. In primary sarcomas in older women and in men with continued growth and recurrence, there was an increase in diene conjugates (DC). In men over 45 years of age, there was an increase in SOD, TPA, and GPx. Women of the older age group were characterized by activation of SOD and GPx, expressed in the relapsed process to a significantly greater extent than in men, and an increase in RG was observed in women. The increase in both components of the glutathione system and SOD activity was especially significant in the development of relapses in women for periods exceeding three years, which was accompanied by a decrease in DC content. Conclusions. Neutrophils are characterized by an increase in DC content in patients of both sexes in the older age group with primary and recurrent STS, with its highest content in men with continued growth and relapses. GPx activity, increased in both men and women in the older age group in all variants of STS development, may play an important role in the antioxidant protection of blood cells in STS. Thus, the most pronounced activation of GPx, accompanied by a maximum increase in reduced glutathione and activation of SOD, contributes to a decrease in the level of DC and the absence of MDA increase in women with slow development of recurrences.

Detection and Differentiation of Local Recurrence of Soft Tissue Sarcoma against the Background of Postoperative Changes Using Echography

Introduction: Early detection of relapses of soft tissue sarcoma can reduce the risk of reoperation and improve oncological outcomes.Material and methods: A multimodal ultrasound examination of 108 soft tissue sites of different localizations was performed, in which earlier (with an interval of 12–62 months after the previous operation) malignant tumors of different histological affiliation were removed.Results: In 37 (34.3 %) observations against the background of postoperative changes, local relapses of neoplasms were revealed. Echographic symptoms that allow differentiating tumor growth and imitating its non-tumor changes have been determined.Conclusions: The most reliable manifestation of the recurrence of the tumor process is a local, uneven strengthening of the vascular pattern directly behind the contour of the neoplasm in its immediate tissue environment.

Patterns of Local Recurrence and Risk of Skin Recurrence in Soft Tissue Sarcomas After Surgical Resection

Although there is a theoretical risk of skin seeding during surgical resection of soft tissue sarcomas (STSs), current consensus guidelines recommend against routine use of bolus during radiation therapy (RT). However, the risk of skin recurrence has not been systematically assessed. We aimed to assess the patterns of local recurrence (LR) in patients with STS treated with surgery with or without RT. We performed a retrospective analysis of adults with STSs evaluated at our institution between 2007 and 2021. For patients who developed LR, the depth was evaluated. Progression-free survival and overall survival were analyzed from time of first LR using the Kaplan-Meier method. Cumulative incidence of distant metastasis was calculated with competing risk analysis from date of LR. Of the 206 patients evaluated, 20 had LR (9.7%). Among patients with LR, 5 patients (25.0%) were treated with surgery alone and 15 patients (75.0%) with surgery and RT. In patients treated with RT, 46.7% had preoperative RT, 53.3% had postoperative RT, and bolus was used in 46.7%. Surgical margins were close (<1 mm) in 4 patients (20.0%) and positive in 10 patients (50.0%). LR occurred in the deep subfascial tissue in 9 patients (45%), subcutaneous tissue in 10 patients (50.0%), and skin in 1 patient (5.0%). The patient with a skin recurrence was treated with surgery alone, and the tumor involved the skin at presentation. In patients treated with RT, LR occurred within the RT field in 13 patients (86.7%). At 1 year after LR, progression-free survival was 70.3%, overall survival was 81.7%, and cumulative incidence of distant metastasis was 5.9%. Skin recurrences were rare after surgical resection of STSs and only occurred in a tumor that involved the skin at initial presentation. These findings support current recommendations against routine use of bolus in STSs not involving the skin at presentation.

1953P Prognostic value of pretreatment inflammatory markers and other clinicopathological factors for early recurrence in soft tissue sarcoma

1953P Prognostic value of pretreatment inflammatory markers and other clinicopathological factors for early recurrence in soft tissue sarcoma

Patterns of local recurrence and risk of skin recurrence in soft tissue sarcomas after surgical resection.

Soft tissue sarcomas (STSs) are rare, heterogeneous tumors primarily managed surgically with radiotherapy (RT) added to improve local control. Although there is a theoretical risk of skin seeding at the time of surgery, current ASTRO Clinical Practice Guidelines recommend against routine use of bolus during pre-operative or post-operative radiotherapy for STS due to increased risk of skin toxicity without clear benefit. However, in the modern era with contemporary treatment planning techniques, the risk of skin recurrence has not been assessed. We performed a detailed analysis of the patterns of local recurrence (LR) in patients with STS treated with surgical resection with or without RT. We performed a retrospective analysis of 206 adult patients with extremity or trunk STSs evaluated in the Department of Radiation Oncology at our institution over 14 years (2007-2021) and identified all patients with LR. The depth of the recurrence and location relative to the radiation field in patients treated with radiotherapy was evaluated. Progression free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method, and cumulative incidence of distant metastasis (CIDM) was calculated with competing risk analysis from the date of LR. Of the 206 patients evaluated, 20 experienced a LR after surgical resection with or without RT. Among patients with a LR, 5 patients (25.0%) were treated with surgery alone and 15 patients (75.0%) received surgery and RT. In patients treated with RT, 46.7% had pre-operative RT, 53.3% had post operative RT, and bolus was used in 5 patients (33.3%). Surgical margins were close (<1mm) in 4 patients (20.0%) and positive in 10 patients (50.0%). Tumor grade was intermediate/high in 15 patients (75%) and the median tumor size was 9 cm (range 5-12). LR occurred in the muscle in 8 patients (40%), subcutaneous tissue in 11 patients (55.0%), and skin in 1 patient (5.0%). The patient with a skin recurrence was treated with surgery alone and the tumor involved the skin at presentation. In the patients treated with RT, LR occurred within radiation field in 10 patients (66.7%). Median follow up time after local recurrence was 12.9 months. At 3 years after LR, PFS was 43.9%, OS was 81.7%, and CIDM was 16.7%. Skin recurrences were exceedingly rare after surgical resection of STSs, and only occurred in a tumor that involved the skin at initial presentation. Due to the increased dose to the normal skin and subcutaneous tissues when bolus is used, which increases risk of toxicity, these findings support current recommendations against routine use of bolus in STSs not involving the skin at presentation.

Multiparametric MRI for the Assessment of Treatment Effect and Tumor Recurrence in Soft-tissue Sarcoma of the Extremities

Soft-tissue sarcomas are a rare and complex group of malignant tumors. Advanced MRI sequences such as diffusion-weighted imaging (DWI) and perfusion-weighted imaging/dynamic contrast enhancement (PWI/DCE) can provide valuable tumor characterization and treatment response assessment. In the case of archetypical cellular tumors such as Pleomorphic Undifferentiated sarcoma (UPS), Good responders often display right-side displacement of the ADC intensity histogram, resulting in increased ADC-mean and decreased kurtosis and Skewness compared with Baseline and poor responders’ more left-sided curve. The PWI/DCE pattern most often associated with a good response is the presence of a “capsular-like” enhancement and a TIC type 2. Sarcoma hemorrhage patterns on SWI emerge during treatment, including “interstitial,” globular,” “luminal,” and incomplete and complete “peripheral ring-like” tumor wall hemosiderin impregnation. Treatment-induced bleeding is typically associated with low SWI-mean values and a left-sided intensity histogram with positive Skewness. During post-surgical surveillance, DCE MR imaging can reliably distinguish recurrent sarcoma from post-surgical scarring. TICs III, IV, and V raise the suspicion of local tumor recurrence, while TIC type II usually represents benign post-operative change such as granulation tissue. Advanced MRI is an essential tool for assessing sarcomas during and after therapy.

Redox status of blood lymphocytes in patients with soft tissue sarcomas

Introduction. The proven significance of free radical disorders in oncopathology determines the relevance of their study in soft tissue sarcomas (STS), which are characterized by a tendency to recurrence and high mortality of patients.Aim. To study the indicators of free radical oxidation and antioxidant protection in blood lymphocytes in primary and recurrent STS, depending on the sex and age of patients.Materials and methods. In 51 patients with primary STS, T2bN0M0 (17 men and 34 women) and in 34 patients (14 men and 20 women) with relapses, the level of lipid peroxidation products – malondialdehyde and diene conjugates, activities of superoxide dismutase and glutathione peroxidase, total peroxidase activity, the level of reduced glutathione were studied by spectrophotometric methods. Patients were divided by age: ≤45 years and &gt;45 years. The comparison groups (donors) consisted of 12 men and 17 women divided into the same age subgroups.Results. In men &gt;45 years old with primary sarcomas, there was an increase in diene conjugates by 2.2 times, with relapses by 2.4 times, and in young men - only with relapses by 2.6 times. The level of malondialdehyde in men did not change with primary sarcomas, with relapses it was reduced in both age groups by 2.4–2.6 times. In women with primary STS, there was an increase in most of the studied parameters in both age groups by 1.6–1.9 times. The increase in diene conjugates level and superoxide dismutase activity was the most pronounced (&gt;3 times) in patients of the older age group. The increase in glutathione peroxidase activity in primary STS in young women was 2.3 times, and in the older age group in patients of both sexes it was 5 times. In half of the women with relapses developed no earlier than 3 years after treatment, a decrease in both lipid peroxidation products by 2.6–3.4 times was found, and in all women almost 4-fold activation of superoxide dismutase and 8-fold glutathione peroxidase with an increase in the level of reduced glutathione by 7 times took place, which was significantly higher than in men. For women of the older age group, a 3-fold increase in the ratio of superoxide dismutase/total peroxidase activity is characteristic for primary STS and almost 5-fold for recurrence.Conclusion. In primary STS, the activation of lipid peroxidation products and antioxidant enzymes in women is more pronounced than in men. Changes in most indicators are more typical for patients of older age groups, in which relapse was accompanied by a decrease in malondialdehyde in patients of both sexes and maximum activation of superoxide dismutase and glutathione peroxidase in women.

Grade shifts in recurrent canine soft tissue sarcomas and mast cell tumors.

To determine the incidence of histologic grade shift (alteration of grade relative to the original tumor) in recurrent canine soft tissue sarcoma (STS) and mast cell tumor (MCT), and to determine the level of agreement between blinded pathologist review and original histology interpretation of STS and MCT grades. 15 dogs with recurrent cutaneous/subcutaneous STS and 5 dogs with recurrent cutaneous MCT. All included dogs underwent excision of both the primary and recurrent tumors and had tumor samples available for review. The medical records and histology database from a single institution were reviewed, and data were recorded and analyzed. A single board-certified veterinary pathologist performed blinded evaluation of all excisional tumor samples, including both primary and recurrent disease, and these were evaluated independently and in conjunction with initial pathologic diagnoses. Based on single pathologist review, 7 of 15 (46.7%) dogs with recurrent STS had grade shift characterized by a higher or lower recurrent tumor grade in 4 of 7 and 3 of 7 cases, respectively, and 1 of 5 dogs with recurrent MCT had grade shift characterized by an increased grade of the recurrent tumor. Variability in reported grade between original histology report and pathologist review occurred for 13 of 30 (43.3%) STS excisional biopsy samples and 0 of 10 MCT excisional biopsy samples. Grade shift has been reported in multiple tumor types in people and has the potential to alter prognosis and treatment recommendations. This is the first study to document this phenomenon in dogs. Additional large-scale studies are needed to determine factors associated with grade shift as well as prognostic significance of grade shift for recurrent canine STS and MCT.

Multiple Flap Transfer for Multiple Local Recurrence of Soft Tissue Sarcoma.

Background and Objectives: Surgical management of local recurrence of soft tissue sarcomas (STS) is still challenging. In this article, we report on multiple flap reconstructions for multiple local recurrences of STS. Their feasibility will be validated by examining clinical cases. Materials and Methods: Patients who underwent multiple flap reconstructions for multiple local recurrences of STS between April 1997 and October 2021 were included in this retrospective study. Patient demographics, tumor characteristics, surgical characteristics, and postoperative complications were examined. Results: Twenty operations of eight patients were identified. The location of the defects was the back in two, the buttock in two, the groin in two, and the lower extremities in two. The average total number of wide resections was 4.0 and the average total number of flap reconstructions was 2.5. The average follow-up period was 109.4 months. The average size of the defect was 102.4 cm2 and the average flap size was 15.7 × 10.8 cm. The histological diagnoses were malignant fibrous histocytoma (MFH) in eight operations, osteosarcoma in two operations, myxoid liposarcoma in two operations, undifferentiated pleomorphic sarcoma (UPS) in six operations, and myxofibrosarcoma (MFS) in one operation. Of twelve subsequent operations, the resection of the previously transferred flap was performed in six operations (50%). The occurrence of take back, flap complications, and donor-site complications in the primary operation group was 25%, 25%, and 12.5%, respectively. The occurrence of take back, flap complications, and donor-site complications in the second and subsequent operation group was 0%, 0%, and 16.7%, respectively. Conclusions: Multiple operations including wide resections followed by flap reconstructions for multiple local recurrences are feasible. Reconstructive surgeons should choose the options of the flaps considering the future local recurrence for tumors with a high risk of recurrence.

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.

Impact of postoperative baseline MRI on diagnostic confidence and performance in detecting local recurrence of soft-tissue sarcoma of the limb

ObjectiveTo evaluate the impact of a postoperative baseline (PB) MRI on diagnostic confidence and performance in detecting local recurrence (LR) of soft-tissue sarcoma (STS) of the limb.Materials and methodsA total of 72 patients (8 with LR, 64 without LR) with primary STS of the limb were included. Routine follow-up MRI (1.5 T) at 6 and approximately 36 months (meanLR: 39.7 months; meanno LR: 34.9 months) after multimodal therapy or at time of LR were assessed by three independent readers using a 5-point Likert scale. Furthermore, the following imaging parameters were evaluated: presence of a mass, signal characteristics at T2- and T1-weighted imaging, contrast enhancement (CE), and in some of the cases signal intensity on the apparent diffusion coefficient (ADC). U-test, McNemar test, and ROC-analysis were applied. Interobserver reliability was calculated using Fleiss kappa statistics. A p value of 0.05 was considered statistically significant.ResultsThe presence of a PB MRI significantly improved diagnostic confidence in detecting LR of STS (p < 0.001) and slightly increased specificity (mean specificity without PE 74.1% and with presence of PB MRI 81.2%); however, not to a significant level. The presence of a mass showed highest diagnostic performance and highest interreader agreement (AUC [%]; κ: 73.1–83.6; 0.34) followed by T2-hyperintensity (50.8–66.7; 0.08), CE (52.4–62.5; 0.13), and T1-hypointensity (54.7–77.3; 0.23). ADC showed an AUC of 65.6–96.6% and a κ of 0.55.ConclusionThe presence of a PB MRI increases diagnostic confidence in detecting LR of STS of the limb.

Editorial Comment: Value of MRI Surveillance for the Detection of Locally Recurrent Soft-Tissue Sarcomas.

Editorial Comment: Value of MRI Surveillance for the Detection of Locally Recurrent Soft Tissue SarcomasShaifali Kaushik, MD1Audio Available | Share

Abstract CT038: Comprehensive molecular characterization of clinical response to durvalumab plus pazopanib combination in patients with advanced soft tissue sarcomas: A phase 2 clinical trial

Abstract We aimed to determine the activity of the anti-VEGF receptor tyrosine-kinase inhibitor, pazopanib, combined with the anti-PD-L1 inhibitor, durvalumab, in soft tissue sarcoma (STS). Further, we performed molecular characterisation with whole exome and transcriptomic sequencing to identify the determinants of response. In this single-arm, phase 2 trial (NCT#03798106), we enrolled patients with metastatic and/or recurrent STS who had received up to two previous lines of systemic anticancer therapy and had at least one measurable lesion. Treatment consisted of pazopanib 800 mg orally, administered once a day, continuously, and durvalumab 1500 mg administered via intravenous infusion once every 3 weeks. The primary endpoint was the overall response rate. Between September 2019 and October 2020, fourteen (30.5%) of the 46 evaluable patients showed an objective response, including in alveolar soft-part sarcoma, angiosarcoma, undifferentiated pleomorphic sarcoma, and desmoplastic small round cell tumour. During a median follow-up period of 18.4 months, the median progression-free survival (PFS) was 7.7 months (95% confidence interval: 5.7-10.4). The common treatment-related adverse events of grades 3-4 included neutropenia (n = 9), elevated aspartate aminotransferase (n = 7) and alanine aminotransferase (n = 5) levels, and thrombocytopenia (n = 4). In the exploratory analysis, the B lineage signature was a significant key determinant of overall response (P=0.014). In situ analysis also showed that tumours with high CD20+ B cell infiltration and vessel density had a longer PFS than those with low B cell infiltration and vessel density (P=6.5 × 10−4) as well as better response (50% vs 12%, P=0.019). In conclusion, durvalumab combined with pazopanib demonstrated promising efficacy in an unselected STS cohort, with a manageable toxicity profile. Our findings provide insights into combined high B cell infiltration and vessel density as potentially relevant biomarkers for the selection of patients who may benefit to a greater extent from PD-L1 blockade and VEGF inhibitor combination. Citation Format: Hee Jin Cho, Kum-Hee Yun, Su-Jin Shin, Young Han Lee, Seung Hyun Kim, Wooyeol Baek, Yoon Dae Han, Sang Kyum Kim, JooHee Lee, Iksung Cho, Heounjeong Go, Jiwon Ko, Inkyung Jung, Min Kyung Jeon, Hyang Joo Ryu, Sun Young Rha, Hyo Song Kim, Hyun Jung Jun. Comprehensive molecular characterization of clinical response to durvalumab plus pazopanib combination in patients with advanced soft tissue sarcomas: A phase 2 clinical trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT038.

Predicting risk of metastases and recurrence in soft-tissue sarcomas via Radiomics and Formal Methods.

Soft-tissue sarcomas (STSs) of the extremities are a group of malignancies arising from the mesenchymal cells that may develop distant metastases or local recurrence. In this article, we propose a novel methodology aimed to predict metastases and recurrence risk in patients with these malignancies by evaluating magnetic resonance radiomic features that will be formally verified through formal logic models. This is a retrospective study based on a public dataset evaluating MRI scans T2-weighted fat-saturated or short tau inversion recovery and patients having "metastases/local recurrence" (group B) or "no metastases/no local recurrence" (group A) as clinical outcomes. Once radiomic features are extracted, they are included in formal models, on which is automatically verified the logic property written by a radiologist and his computer scientists coworkers. Evaluating the Formal Methods efficacy in predicting distant metastases/local recurrence in STSs (group A vs group B), our methodology showed a sensitivity and specificity of 0.81 and 0.67, respectively; this suggests that radiomics and formal verification may be useful in predicting future metastases or local recurrence development in soft tissue sarcoma. Authors discussed about the literature to consider Formal Methods as a valid alternative to other Artificial Intelligence techniques. An innovative and noninvasive rigourous methodology can be significant in predicting local recurrence and metastases development in STSs. Future works can be the assessment on multicentric studies to extract objective disease information, enriching the connection between the radiomic quantitative analysis and the radiological clinical evidences.

Abstract 203: A characterization of drug sensitivity and resistance in sarcoma

Abstract Bone and soft tissue sarcomas are a rare and diverse family of malignancies. Sarcomas disproportionally impact young patients, and most subtypes have limited therapeutic options. Given the rarity of these tumors and their heterogenous nature, there is a need for developing clinically relevant models to broadly characterize the landscape of drug resistance and sensitivity in sarcoma in order to identify effective therapies. We leverage patient-derived tumor organoids (PDTOs) to create models across an array of bone and soft tissue sarcomas. We have procured n=193 specimens from n=127 patients undergoing biopsies or surgical resections at UCLA Health hospitals and successfully generated PDTOs from over 100 samples so far originating from primary, recurrent, or metastatic bone and soft tissue sarcomas. We performed molecular and histologic characterization to compare the PDTOs with the parent tumor and monitored PDTOs growth using a machine learning-based imaging pipeline (Al Shihabi et al, 2022). Our results show that sarcoma PDTOs closely resemble the tumor of origin in their molecular features and exhibit diverse growth patterns across subtypes. We leveraged our existing organoid high-throughput drug screening pipeline (Phan et al, 2019) to perform functional screenings of chemotherapies, targeted agents, and combination therapies, with results within one week from surgery. By screening a large number of samples, we could identify patterns of response with respect to diagnosis, prior treatment, patient age, lesion type, and disease trajectory. We observe tumor-specific susceptibilities with high heterogeneity both across and within sarcoma subtypes. As an example, we will focus on osteosarcoma, a bone tumor common in the pediatric and AYA population. We characterized PDTOs from n=33 osteosarcoma specimens and observed significant heterogeneity in response to NCCN-recommended therapies, suggesting that some patients may benefit from a personalized selection of approved therapeutic regimens. Finally, we compare functional and genomic screening to show how drug sensitivity and resistance characterization can facilitate optimal drug selection, avoid ineffective therapies, and mirror patient outcomes. Citation Format: Ahmad Al Shihabi, Peyton J. Tebon, Huyen T. Nguyen, Jomjit Chantharasamee, Sara Sartini, Ardalan Davarifar, Alexandra Jensen, Miranda Diaz-Infante, Hannah Cox, Alfredo Gonzalez, Nasrin Tavanaie, Sarah Dry, Arun Singh, Bartosz Chmielowski, Joseph G. Crompton, Anusha Kalbasi, Fritz C. Eilber, Francis J. Hornicek, Nicholas Bernthal, Scott D. Nelson, Paul C. Boutros, Noah Federman, Jane Yanagawa, Alice Soragni. A characterization of drug sensitivity and resistance in sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 203.