Sarcoma Center Research Articles

Vascularized Bone Graft Reconstruction Following Bone Tumor Resection at a Multidisciplinary Sarcoma Center: Outcome Analysis.

Limb-sparing procedures are frequently applied to improve patient outcomes. The use of vascularized bone grafts is associated with significant improvements in oncologic safety and functional satisfaction. This study highlights the clinical outcomes following tumor resection combined with vascularized bone graft reconstructions. Twenty-five free vascularized bone grafts (17 fibulas, 5 iliac crests, 3 medial femoral condyles) were assessed with respect to consolidation and hypertrophy, functional and oncologic outcomes, and local complications. The rate of healing of fibular grafts after a median of 5 months was 86%. The rate of achieved unions of iliac crest grafts after a median of 5 months was 80%. In medial femoral condyle bone grafts, union occurred after a median of 4 months. Significant hypertrophy was observed in 13 patients. We identified six complications with highest rates in the fibula-group. Despite the high complications, functional results were highly satisfactory. Vascularized bone grafts represent a reconstructive approach, maintaining long-term functionality and cosmetic satisfaction without compromising tumor recurrence outcomes.

Clinical characteristics of patients with undergoing unplanned excisions of malignant soft tissue tumors.

Malignant soft tissue tumors are rare tumors representing <1% of all malignancies. As these tumors are rare, it is not uncommon that malignant soft tissue tumor excision is performed without the required preoperative imaging, staging, or wide resection margins for sarcomas. The purpose of this study was to investigate the characteristics of patients with undergoing unplanned excisions. Risk factors for tumor recurrence and mortality in patients treated with unplanned excisions were also analyzed. Forty-nine patients who underwent unplanned excision at other hospitals and additional wide excision at our hospital between January 2002 and December 2018 were identified. Among them, 42 patients with follow-up for more than 1year were included in this retrospective study. The relationships between sex, age, tumor depth, histological grade, location, size, surgical margin at additional wide excision, residual tumor, reconstruction, kind of hospital where the primary excision was done (sarcoma vs non-sarcoma center), preoperative examination, chemotherapy, radiation therapy, and oncological outcomes were statistically analyzed. Mean patient age was 57.3years (15-85years) and the mean observation period was 72.5 months (14-181months). This analysis showed 53.8% tumors that underwent unplanned excisions were small (<5cm) and 70.7% tumors were superficial. Multivariate analysis revealed that a positive margin during additional wide excision was significantly associated with a lower 5-year LRFS (p < 0.01). Most of the tumors underwent unplanned excisions were small (<5cm) and superficial. Surgeons should be aware that a positive margin during additional wide excision is an independent risk factor for local recurrence.

Regional variation in the survival of patients with a soft-tissue sarcoma of the extremity and trunk wall under a centralized care system : what has been the impact of national policies in the UK?

While a centralized system for the care of patients with a sarcoma has been advocated for decades, regional variations in survival remain unclear. The aim of this study was to investigate regional variations in survival and the impact of national policies in patients with a soft-tissue sarcoma (STS) in the UK. The study included 1,775 patients with a STS who were referred to a tertiary sarcoma centre. The geographical variations in survival were evaluated according to the periods before and after the issue of guidance by the National Institute for Health and Care Excellence (NICE) in 2006 and the relevant evolution of regional management. There had been a significant difference in survival between patients referred from the North East, North West, East Midlands, West Midlands, South West, and Wales in the pre-NICE era (five-year disease-specific survival (DSS); South West, 74% vs North East, 47% (p = 0.045) or West Midlands, 54% (p = 0.049)), which was most evident for patients with a high-grade STS. However, this variation disappeared in the post-NICE era, in which the overall DSS for high-grade STS improved from 47% to 68% at five years (p < 0.001). Variation in the size of the tumour closely correlated with the variation in DSS, and the overall size of the tumour and incidence of metastasis at the time of diagnosis also decreased after the national policies were issued. The survival of patients with a STS improved and regional variation corrected after the introduction of national policies, as a result of a decreasing size of tumour and incidence of metastasis at the time of diagnosis, particularly in patients with a high-grade STS. This highlights the positive impact of national guidelines on regional variation in the presentation, management, and outcome in patients with a STS. Cite this article: Bone Joint J2021;103-B(9):1541-1549.

Efficacy of Sirolimus Treatment in PEComa-10 Years of Practice Perspective.

Perivascular epithelioid cell tumors (PEComa) represent a family of rare mesenchymal tumors resultant from deregulation in mTOR pathway activity. The aim of this study is to evaluate the long-term efficacy of targeted PEComa treatment. We reviewed all consecutive patients with PEComa who started systemic treatment with sirolimus in our reference sarcoma center between January 2011 and August 2020. Histopathology of PEComa was reviewed and confirmed in all cases by a designated sarcoma pathologist. Any surviving progression-free patients were censored at the last follow-up (31 March 2021). Survival curves were calculated according to Kaplan–Meier method and compared with the log-rank test or a Cox proportional hazard model. Fifteen (12 females and 3 males) consecutive PEComa patients were treated. The median age of patients treated systemically was 50 years. Median progression-free survival (PFS) was 4.9 months (95% CI: 3.8-NA) for first-line chemotherapy and was not reached (95% CI: 42.0-NA) for sirolimus as first-line therapy. There was one objective response (OR) in the chemotherapy group. The OR rate reached 73% (11/15 cases) for sirolimus regardless of the treatment line. All patients archived disease control. Three patients died due to disease progression after 55, 32, and 32 months since metastatic disease diagnosis. After a median follow-up of 55.7 (range: 3.2–220) months, the 5 yr OS was 65% (CI 95% 39–100). Our study is the largest single-institution report on PEComa systemic targeted therapy and fills the gap in the field of advanced PEComa care since the FDA/EMEA approval of sirolimus.

Predictive Value of Preoperative Controlling Nutritional Status Score Combined with Fibrinogen-Albumin Ratio in Postoperative Local Recurrence-Free Survival of Patients with Retroperitoneal Liposarcoma.

BackgroundPrevious studies have shown that nutrition and systemic inflammation plays an essential role in the development of soft tissue sarcoma. However, few studies have explored the association of clinicopathologic features and local recurrence with nutritional and inflammatory markers in retroperitoneal liposarcoma (RPLS). This study sought to evaluate the prognostic value of the preoperative nutritional and inflammatory markers for local recurrence-free survival (LRFS) among surgical RPLS patients.MethodsThe study included 111 RPLS patients who underwent surgery between May 2010 and June 2019 at the Peking University Cancer Hospital Sarcoma Center. Time-dependent receiver operating characteristic (time-ROC) curve analysis was conducted to evaluate the ability of markers to predict LRFS. The associations of the CONUT-FAR score with clinicopathological variables and LRFS were evaluated.ResultsIn the time-ROC curve analysis, the CONUT-FAR score was superior to other nutritional and inflammatory markers in predicting LRFS. The CONUT-FAR score was the only nutritional and inflammatory marker that independently predicted LRFS in the multivariate analysis, and patients with a high CONUT-FAR score (> 11) showed significantly decreased LRFS. Although the CONUT-FAR score failed to discriminate patients with low grade (G1) (p = 0.327) or undergoing incomplete (R2) resection (p = 0.072), it stratified patients with high grade (G2 and G3) or undergoing complete resection (R0/R1) into subgroups with significantly distinct LRFS (p < 0.001). The CONUT-FAR score also showed good clinical utility among patients with different clinical characteristics.ConclusionThe preoperative CONUT-FAR score reflects both nutritional and inflammatory factors and is an effective predictor of LRFS for surgical RPLS patients.

Economic burden and health-related quality of life in tenosynovial giant-cell tumour patients in Europe: an observational disease registry

BackgroundTenosynovial Giant-Cell Tumour (TGCT) is a benign clonal neoplastic proliferation arising from the synovium, causing a variety of symptoms and often requiring repetitive surgery. This study aims to define the economic burden—from a societal perspective—associated with TGCT patients and their health-related quality of life (HRQOL) in six European countries.MethodsThis article analyses data from a multinational, multicentre, prospective observational registry, the TGCT Observational Platform Project (TOPP), involving hospitals and tertiary sarcoma centres from six European countries (Austria, France, Germany, Italy, the Netherlands, and Spain). It includes information on TGCT patients’ health-related quality of life and healthcare and non-healthcare resources used at baseline (the 12-month period prior to the patients entering the registry) and after 12 months of follow-up.Results146 TGCT patients enrolled for the study, of which 137 fulfilled the inclusion criteria. Their mean age was 44.5 years, and 62% were female. The annual average total costs associated with TGCT were €4866 at baseline and €5160 at the 12-month follow-up visit. The annual average healthcare costs associated with TGCT were €4620 at baseline, of which 67% and 18% corresponded to surgery and medical visits, respectively. At the 12-month follow-up, the mean healthcare costs amounted to €5094, with surgery representing 70% of total costs. Loss of productivity represented, on average, 5% of the total cost at baseline and 1.3% at follow-up. The most-affected HRQOL dimensions, measured with the EQ-5D-5L instrument, were pain or discomfort, mobility, and the performance of usual activities, both at baseline and at the follow-up visit. Regarding HRQOL, patients declared a mean index score of 0.75 at baseline and 0.76 at the 12-month follow-up.ConclusionThe results suggest that TGCT places a heavy burden on its sufferers, which increases after one year of follow-up, mainly due to the healthcare resources required—in particular, surgical procedures. As a result, this condition has a high economic impact on healthcare budgets, while the HRQOL of TGCT patients substantially deteriorates over time.

Role of Radiation Therapy for Newly Diagnosed Retroperitoneal Sarcoma.

Soft tissue sarcomas (STS) are rare, aggressive, and heterogenous tumors, comprising approximately 1% of adult cancers with over 50 different subtypes. The mainstay of treatment for retroperitoneal sarcomas (RPS) includes surgical resection. The addition of radiation therapy (RT), either preoperatively or postoperatively, has been used to potentially decrease the risk of local recurrence. The recently published results from STRASS (EORTC-STBSG 62092-22092), which randomized patients to receive or not receive preoperative radiation, indicate no abdominal recurrence-free survival benefit (primary endpoint) nor overall survival benefit to date from the addition of preoperative RT prior to surgical resection in patients with RPS. Keeping in mind caveats of subgroup analyses, the data show a significant reduction in local recurrence with radiation therapy in resected patients and non-significant trends toward improved abdominal recurrence-free survival in all patients and improved local control and abdominal recurrence-free survival in patients with liposarcoma and low-grade sarcoma. Given the high rate of local failure with surgery alone, it is possible that higher RT dose and/or selective RT dose painting may improve outcomes. Prior to treatment, the authors encourage multidisciplinary review and discussion of management options at a sarcoma center for patients with RPS. Selective use of RT may be considered for patients at high risk of local recurrence.

Telangiectatic soft tissue sarcoma and chronic expanding haematoma: a comparative review of MRI features.

Soft tissue sarcomas containing a dominant component of haemorrhage are known to be aggressive tumours associated with a poor prognosis. Importantly, the clinical behaviour and imaging characteristics of extensively haemorrhagic soft tissue sarcomas (also termed telangiectatic soft tissue sarcomas) can resemble those of benign haematomas, particularly those that continue to expand over a prolonged period, so-called chronic expanding haematomas (CEH). The following review evaluates the current literature to identify the clinical, imaging and pathological characteristics of telangiectatic soft tissue sarcomas and to determine features that may help distinguish them from CEH. Ultimately, we suggest that lesions with sizeable regions of internal haemorrhage should be regarded with a high degree of suspicion for underlying malignancy and require referral to a tertiary sarcoma centre, where a carefully planned approach to biopsy and follow-up is needed to avoid errors in diagnosis.

Cat at home? Cat scratch disease with atypical presentations and aggressive radiological findings mimicking sarcoma, a potential diagnostic pitfall

Background and purpose — Cat scratch disease (CSD) is a self-limiting disease caused by Bartonella (B.) henselae. It is characterized by granulomatous infection, most frequently involving lymph nodes. However, it can present with atypical symptoms including musculoskeletal manifestations, posing a diagnostic challenge. We describe the prevalence and demographics of CSD cases referred to a sarcoma center, and describe the radiological, histological, and molecular findings. Patients and methods — Our cohort comprised 10 patients, median age 27 years (12–74) with clinical and radiological findings suspicious of sarcoma. Results — 7 cases involved the upper extremities, and 1 case each involved the axilla, groin, and knee. B. henselae was found in 6 cases tested using polymerase chain reaction and serology in 5 cases. 9 cases were soft tissue lesions and 1 lesion involved the bone. 1 patient had concomitant CSD with melanoma metastasis in enlarged axillary lymph nodes. On MRI, 5 soft tissue lesions were categorized as probably inflammatory. In 3 cases, with still detectable lymph node structure and absent or initial liquefaction, the differential diagnosis included lymph node metastasis. A sarcoma diagnosis was suggested in 4 cases. The MRI imaging features of the bone lesion were suspicious of a bone tumor or osteomyelitis. Interpretation — Atypical imaging findings cause a diagnostic challenge and the differential diagnosis includes malignant neoplasms (such as sarcoma or carcinoma metastasis) and other infections. The distinction between these possibilities is crucial for treatment and prognosis.

CRANIOFACIAL OSTEOSARCOMA: A CASE REPORT

<h3>Background</h3> Osteosarcoma is the most common primary bone tumor, with 10% of cases affecting the head and neck. Demographics of head and neck osteosarcoma are different from those elsewhere in the musculoskeletal system. Prognosis is strongly dependent on negative resection margins with the use of neoadjuvant chemoradiotherapy in select cases. <h3>Description</h3> We present a case of a 58-year-old male nonsmoker patient who presented with a lump in his left upper jaw. Clinical examination revealed an exophytic mass in the upper left tuberosity of the maxilla suspicious for squamous cell carcinoma with no associated lymphadenopathy. <h3>Findings</h3> Radiological investigations revealed a metabolically active left maxillary lesion with destruction of the maxillary sinus. Histologic examination of a superficial biopsy initially suggested a proliferative fibro-osseous lesion; however, a second deeper biopsy was diagnostic of osteosarcoma, and the patient was referred to a sarcoma center. Immunohistochemistry showed AE1/AE3 and CK(MNF.116) positivity in occasional cells with a Ki67 proliferation index of 60%. This was diagnostic of grade 2-3 osteosarcoma. Multidisciplinary management of the patient included neoadjuvant chemotherapy and total maxillectomy and dental prosthetic rehabilitation. The patient is still under follow-up. <h3>Conclusions</h3> This case of primary osteosarcoma of the maxilla is rare and scarcely reported in the literature. Clinical differential diagnoses include squamous cell carcinoma, and histologic differential diagnosis includes fibro-osseous proliferative lesions in undersampled cases. It is important to consider osteosarcoma in destructive lesions, as it requires prompt and early specialist intervention to maximize the chances of negative surgical margins, which is the mainstay of treatment for this disease for prognosis.

Prosthesis or osteosynthesis for the treatment of a pathological hip fracture? A nationwide registry-based cohort study

AimsHow endoprosthetic replacement compares to osteosynthesis in the treatment of pathologic hip fractures as far as functional outcome and use of healthcare resources is concerned remains largely unknown. We aimed to investigate this in a nationwide registry. MethodsWe analyzed the functional outcome after surgery for a pathological fracture of the hip in terms of post-operative pain and ambulatory capacity. The preferred surgical method depending on the level of the treating unit was also examined. Furthermore, we documented the length of hospital stay and the patterns of discharge and compared them between these two methods. ResultsPatients operated with an endoprosthesis reported significantly lower pain at follow-up. Both methods (endoprosthetic replacement and osteosynthesis) were equally effective in restoring the ambulatory capacity and demanded a similar length of stay in hospital. Orthopaedic surgeons working in hospitals with dedicated sarcoma teams were more likely to use a prosthesis rather than osteosynthesis, when compared to surgeons working at other university hospitals or emergency hospitals. ConclusionEndoprosthetic replacement results in a better functional outcome in terms of post-operative pain without consuming more healthcare resources. Orthopaedic surgeons working in hospitals with sarcoma centers are more likely to use prostheses as compared to surgeons working at hospitals where dedicated musculoskeletal oncology teams are not available.

Surgical management of soft tissue tumors of the abdominal wall: A retrospective study in a high-volume sarcoma center.

The aim of the study is to evaluate functional and oncological outcomes of patients undergoing abdominal wall soft tissue tumors (AWSTT) surgery. All consecutive patients that underwent surgery for malignant and intermediate AWSTT from 1999 to 2019 were retrospectively analyzed. Ninety-two patients were identified, 20 (22%) operated on for a desmoid tumor and 72 (78%) for a soft tissue sarcoma (STS). Fifty-two patients (57%) had in toto resection of the abdominal wall (from the skin to the peritoneum) and 9 (10%) required simultaneous visceral resection. The closure was direct in 28 patients (30%) and requiring a mesh, a flap or a combination of the two in respectively 42, 16, and 6 patients (47%, 17%, 6%). The postoperative complications rate was 26%. Thirteen patients (14%) developed an incisional hernia after a median delay of 27 months. After a median follow-up of 40 months, out of the 72 patients operated on for STS, 7 (10%) developed local recurrence and 11 (15%) distant recurrence. The median recurrence-free and overall survivals were 61 and 116, months respectively. Management of AWSTT requires extensive surgery but allows good local control with an acceptable rate of incisional hernia.

Surgery in soft tissue sarcoma: the thin line between a surgical or more conservative approach.

Surgery is the primary treatment for localized, clinically resectable soft tissue sarcoma (STS). Chemotherapy and radiotherapy, administered in the pre- or post-operative settings, have important ancillary roles in the multimodal management of primary STS. Some sarcoma centers also employ locoregional therapies such as isolated limb perfusion and deep wave hyperthermia in multimodal therapy. In advanced or metastatic STS, surgery is recommended when complete resection is feasible. Nevertheless, in certain situations there is thin line between a surgical or non-surgical approach, generally related to STS histological type/subtype, disease stageand technical considerations. In advanced STS, factors favoring surgery are isolated oligometastatic disease, long disease-free interval, suitable histology, response to chemotherapy and high probability of a complete resection.

Apatinib plus ifosfamide and etoposide for relapsed or refractory osteosarcoma: A retrospective study in two centres.

For osteosarcoma that progresses following first-line chemotherapy, prognosis remains poor although anti-angiogenesis tyrosine kinase inhibitors (TKIs) have been verified to prolong progression-free survival. Apatinib has led to positive responses in the treatment of refractory osteosarcoma. However, it demonstrates only short-lived activity, and the disease control rate of musculoskeletal lesions is worse compared with that of pulmonary lesions. This treatment failure has been partly overcome by the addition of ifosfamide and etoposide (IE). The present study retrospectively compared the activity of apatinib + IE in relapsed or refractory osteosarcoma in two sarcoma centres in China. The included patients had received a combination of apatinib 500 mg (orally) daily and the IE regimen (n=33) between June 3 2017 and July 17 2020. The tumour burden was considerable in these patients: 16/33 (48.5%) Patients had lung and musculoskeletal lesions, and 31/33 (93.9%) patients had progressed to two lines of therapies at baseline. With a median follow-up duration of 28.4 [interquartile range (IQR), 16.1–38.3] months, 21/33 (63.6%) patients had objective responses, and the median event-free survival was 11.4 (IQR, 6.7–18.4) months. The median overall survival time was 19.8 (IQR, 13.1–30.6) months. At the last follow-up, 16/33 patients had tumour downstaging, and all lesions had been completely resected. For osteosarcoma with multiple sites of metastasis, apatinib + IE demonstrated clinically meaningful antitumor activity and delayed disease progression in patients with recurrent or refractory osteosarcoma after failure of chemotherapy. This combination with manageable toxicity deserves further investigation in prospective trials.

Apatinib plus ifosfamide and etoposide (IE) versus IE chemotherapy alone for relapsed or refractory osteosarcoma.

e23502 Background: Results of previous study showed promising objective response but short-lived activity of apatinib in the treatment of osteosarcoma refractory to first-line chemotherapy, from which we observed the disease control of musculoskeletal lesions were worse than pulmonary lesions. This treatment failure has partly been overcome by the addition of Ifosfamide and etoposide in OLIE study. We aimed to retrospectively compare the activity of apatinib in combination with IE in relapsed or refractory osteosarcoma with synchronous patients receiving IE chemotherapy alone in two sarcoma centers in China. Methods: We retrospectively analyzed medical files and radiographic materials of patients with osteosarcoma relapsed or refractory to first-line chemotherapy, who had received combination of apatinib and IE regimen or IE chemotherapy alone between June 3rd, 2017 and July 17th, 2020. Seventy-nine patients were included, of whom 33 patients received apatinib in combination with IE and 46 patients received single IE chemotherapy. Results: Patients’ tumor burden and general status were obviously different between these two groups with 16/33 (48.5%) patients receiving apatinib+IE having both Lung and musculoskeletal lesions at baseline and 39/46 (84.8%) patients receiving single IE having just pulmonary lesions at baseline. However at last follow up 16/33 (48.5%) of patients receiving apatinib+IE had all lesions resected while 23/46 (50.0%) of patients receiving IE alone had their lesions resected, which might partly due to down-staging of the diseases. With median follow-up time of 28.4 (IQR, 16.1-38.3) months, 21/33 (63.6%) patients receiving apatinib+IE had objective responses while 13/46 (28.3%) patients receiving single IE chemotherapy had responses. The median event-free survivals (EFS) were respectively 11.4 (IQR, 6.7-18.4) months for apatinib+IE and 11.2 (IQR, 4.4-21.8) months for IE alone without significant statistical differences (P = 0.47). The overall survival (OS) was obviously different because of disease stage and tumor burden according to Kaplan-Meier analysis with median OS time of 30.4 (IQR, 21.8-not reached) months for IE alone and 19.8 (IQR, 13.1-30.6) months (P = 0.019). Conclusions: For osteosarcoma with multiple sites’ metastasis, apatinib plus IE demonstrated clinically meaningful antitumor activity in patients with recurrent or refractory osteosarcoma after failure of MAP/I chemotherapy or even single apatinib or IE treatment alone, with a positive effect on delaying disease progression. This combination deserves further investigation in prospective trials with manageable toxicity.

Impact of interdisciplinary sarcoma board evaluation on treatment outcome of primary soft-tissue sarcoma patients.

e23540 Background: Early presentation of soft-tissue sarcoma (STS) patients to a specialized sarcoma center including discussion in the interdisciplinary sarcoma board (ISB) prior to surgery is essential to the treatment of sarcomas. This approach significantly improves patient survival and guideline coherence. However, there exists only limited information on the adherence to the recommendations of the ISB. Accordingly, we decided to analyze a STS cohort at a large German sarcoma center focusing on outcome parameters and adherence to quality parameters defined by the German Cancer Society (Deutsche Krebsgesellschaft). Methods: In a retrospective data analysis, we identified n = 230 adult patients presented at the ISB of the Charité–Universitätsmedizin Berlin in Germany from January 2015 until December 2019. Inclusion criteria were as follows: newly diagnosed STS, presentation during first-line therapy and recommendation of at least one treatment modality such as surgery, chemotherapy, radiotherapy, regional hyperthermia or follow-up by the ISB. Clinical and follow up data was collected by using the hospital information system and the outpatient network. Results: Our patient cohort included 53% male and 47% female patients with a median age of 58 years (range 19-96). The majority (86%) showed a localized tumor stage, while 14% already had metastases. In 24% of the cases the sarcomas were classified as low-grade, in 76% as high-grade. Surgery was recommended for 66% of the cases, for 80% of them combined with chemotherapy, radiotherapy or hyperthermia. 14% of the patients received a recommendation for all 4 modalities. For 9% of the patients, chemotherapy alone was recommended. Both overall survival and progression-free survival was significantly higher in the group with complete adherence to the recommendations of the ISB (p &lt; 0.001). The worst prognosis was found in patients unable to adhere to the recommendations due to rapid progression or complications of the therapy (HR for death 15.06, 95%CI 7.94-32.22). If one recommended modality was not carried out, there also was a higher risk of death (HR 4.38, 95%CI 1.75-10.96). Most common reasons were patient refusal or individual decision by the treating physician. A metastasized tumor stage was associated with an increased risk of death (HR 2.62, 95%CI 1.45-4.75). In contrast, neither the histological grading (low vs. high) nor age did influence the mortality significantly. Conclusions: In our cohort of STS patients, survival depends significantly on adherence to the recommendations of the ISB. Our analysis at a German sarcoma center is in line with previous international reports demonstrating the importance of interdisciplinary decisions and therapeutic adherence. We hereby underline the essential role of interdisciplinary approaches in care of STS patients and the effort to implement defined quality parameters.

Quality of life outcomes in sarcoma patients receiving care at a tertiary center.

e23557 Background: Sarcomas are a diverse group of neoplasms that vary greatly in clinical presentation and responsiveness to treatment. Given the differences in the sites of involvement, rarity, and treatment modality, a multidisciplinary approach is required. Previous literature suggests patients with sarcoma suffer from poorer quality of life (QoL) especially physical and functional well-being. This study aims to understand if there is an association between treatment at a tertiary sarcoma center and a difference in QoL. Methods: De-identified data was obtained from the Sarcoma Tissue Repository at University of Iowa. Mixed effects regression models were utilized to evaluate the association between disease and treatment characteristics and QoL. QoL was assessed using the self-report FACT-G questionnaire at 12-, 24-, and 36-months post-diagnosis; overall scores and the 4 well-being subscales (Physical, Emotional, Social, Functional) were calculated. Results: 443 patients were identified. Soft tissue sarcomas were more prevalent (87.6%) than bone (12.4%). 53% of patients received chemotherapy and 38.6% got radiation therapy. Sarcomas were most frequently located in the lower extremities(ext.) (33.1%), followed by abdomen (20.9%), pelvic (13.6%), upper ext. (13.1%), thorax (11.3%), head &amp; neck (7.8%). For ext. sarcoma; lower ext: 144 (71.3%), Upper ext: 58 (28.7%). Patients with extremity sarcoma; 133 had limb sparing and 48 had amputations. FACT-G Scores did not appreciably vary between 12, 24-, and 36-month for any QoL responses. Overall well-being had a mean score reported of 87.7 (sd = 15.7). Social well-being sores averaged 23.5 (5.0). Emotional well-being (EWB) 19.2 (4.1) and functional well-being (FWB) 21.3 (6.1), and physical well-being (PWB) 23.7 (4.6). There was no association between overall, PWB, EWB, or FWB with the histological subtype, radiation treatment, type of limb surgery, or any location in the same patients over time. Chemotherapy treatments were associated with lower well-being in multiple domains; PWB scores being 2.01 points lower, (p &lt; 0.01), EWB scores being 1.27 points lower (p = 0.01) and FWB scores being 1.72 (p = 0.03), and 4.44 points lower overall (p = 0.03), on average, after adjusting for overall changes across time. Patients with ext. sarcoma only overall FACT-G scores differed 6.72 points higher for upper ext. than lower ext (p = 0.04). Conclusions: Overall QoL areas were similar to normative FACT-G scores both overall and specific areas. Having received chemotherapy was associated with lower well-being scores physically, emotionally, functionally, and overall. There were no clinically relevant differences reported in QoL scores between 12-,24-, and 36-months in the same patients. Further work is needed to describe QoL differences among patients with sarcoma at tertiary centers and examine what protective factors may influence patient well-being.

A retrospective study to evaluate the safety and efficacy of anlotinib plus camrelizumab in management of advanced retroperitoneal sarcoma.

e23545 Background: Several studies have demonstrated the antitumor activity of single-agent anlotinib in the treatment of soft tissue sarcoma (STS). However, the most effective results were from cases of alveolar soft part sarcoma (ASPS), which was a rare subtype in retroperitoneal sarcoma (RPS). The therapy of RPS is still dismal. Thus, we evaluated the effectiveness and safety of anlotinib plus camrelizumab for the treatment of RPS. Methods: We retrospectively reviewed the data of 36 patients with advanced/metastatic RPS in Sarcoma Centre of Peking University Cancer Hospital from July 2019 to February 2021. Anlotinib was given 12mg Qd 2 weeks on and 1 week off, and camrelizumab was transfused 200mg at Q3w. Patients that underwent at least 4 cycles of therapy were enrolled in this study. The primary endpoint is objective response rate (ORR) and evaluated according to the irRECIST 1.1 criteria. Results: The pathologic subtypes of enrolled cases include liposarcoma (LP) (n = 16), leiomyosarcoma (LMP) (n = 5), uncertain differentiation sarcoma (n = 7), fibroblastic and myofibroblastic tumours (n = 4), rhabdomyosarcoma (n = 2) and malignant peripheral nerve sheath tumour (MPNST) (n = 2). Two patients (5.6%) achieved CR and 9 patients (25.0%) achieved PR, with an ORR of 30.6%. Eighteen patients (50.0%) achieved SD and 7 patients (19.4%) were evaluated as PD, with the disease control rate (DCR) of 80.6%. The progression-free rate (PFR) at six months was 60.0%. Five patients underwent further radical surgical resection. The two CR cases were diagnosed as dedifferentiated liposarcoma (DDLP) and MDM2 amplified MPNST respectively, and both patients have been under CR status for over 12 months until now. The only grade 3 or higher treatment related adverse event was hypertension (22.2%). Camrelizumab related reactive cutaneous capillary endothelial proliferation (RCCEP) was not observed in this group of patients. Conclusions: The combination of anlotinib and camrelizumab demonstrated encouraging efficacy and safety in the treatment of RPS. A further clinical study with biomarker exploration should be performed in the future.

Retrospective world-wide registry on the efficacy of immune checkpoint inhibitors in alveolar soft part sarcoma: Updated results from sixty patients.

11564 Background: Alveolar soft-part sarcoma (ASPS) is a highly metastasizing ultra-rare sarcoma subtype, frequently affecting young adults. Conventional cytotoxic drugs are not effective in ASPS, but antiangiogenics demonstrated significant improvement in tumor burden reduction and PFS in the only ever conducted comparative trial. Immune check-point (PD-1/PD-L1) inhibitors (ICI) are emerging promising drugs in the therapy of ASPS, from small reported retrospective and prospective series. A world-wide registry has been set up with the aim of exploring the efficacy of ICI in ASPS. Methods: Data from adult patients (pts) diagnosed with ASPS and treated with PD- 1/PD-L1 inhibitors for advanced disease in expert sarcoma centers from Europe, Australia and US was retrospectively collected. IRB approval was obtained. Demographics, data related to treatments and outcome were considered. Radiologic assessment was based on RECIST 1.1. Progression-free (PFS) and overall survival (OS) were calculated with Kaplan-Meier method. An updated analysis of this series is presented here. Results: Sixty ASPS pts (27 female/33 male) with a median age at diagnosis of 25y (range 3-61) were registered. Primary tumor arose in limbs in 47 pts (78%) and 41 pts (68%) were metastatic at diagnosis. 52/60 pts (87%) had received previous systemic therapy (including chemotherapy in 19 pts and antiangiogenics in 47pts), with a median of one previous line (0-6). All pts received ICI for metastatic disease. Immunotherapy regimens consisted of monotherapy in 31 pts (52%) and combination in 29 pts (48%) (23 with an antiangiogenic agent). 29/60 pts (48%) received ICI within a clinical trial. Among the 52 evaluable pts, there was 1 complete response (CR) and 20 partial responses (PR) (ORR 40.4%). After a median follow-up of 21 months -mos- (range 4-59), 37/60 pts have progressed to ICI, with a median PFS of 13.4 mos (95% CI 10.1-16.7). Eleven pts received a subsequent line of ICI with a median PFS of 26 mos (95%CI 0-57). 16 pts have died, being the median OS from ICI initiation 38 mos (95% CI 33-43). The 12-mos and 24-mos OS rates were 94% and 70% respectively. Conclusions: This registry constitutes the largest available series of ASPS treated with immune check-point inhibitors. Our results suggest that treatment with ICI provide long-lasting disease control and prolonged OS in pts with advanced ASPS, an ultra-rare entity with limited active therapeutic options. The results on subsequent ICI lines suggest a lack of cross-resistance among different ICI therapies.

Association of treatment delays with an unfavorable outcome in patients with localized Ewing sarcoma: A retrospective analysis of data from the GPOH Euro-E.W.I.N.G.99 trial.

11502 Background: Outcome in EwS has improved by the implementation of dose or time intense systemic treatment. Aim of the study was evaluate whether treatment delays have impact on outcome of patients with localized Ewing sarcoma (EWS). Methods: Data from 692 patients with a tumor of the extremities, the pelvis, the chest wall and the trunk registered in the international database of the German Society for Pediatric Oncology and Hematology (GPOH) and treated in the Euro-E.W.I.N.G. 99 trial (NCT00020566) were analyzed. All patients underwent surgical treatment after induction chemotherapy. The optimal interval cut-off values for survival analyses were calculated with receiver operating characteristics curves. Hazard ratios (HR) were estimated with respective 95% confidence intervals (CI) in multivariate Cox regression models. Results: As per protocol, patients were to receive six cycles of VIDE induction chemotherapy in 21-day intervals. The duration between induction cycles as per protocol was fulfilled in only 5% of patients. In 72% of patients, the average interval duration between induction chemotherapy cycles was 25 days. Median interval between day 1 of the first induction chemotherapy cycle and definitive tumor surgery was 141 (IQR, 133 – 153) days in patients receiving six VIDE cycles prior to surgery. The optimal cut-off value for survival analyses in these patients amounted to 150 days. Patients with a duration of induction chemotherapy &gt; 150 days were at higher risk to develop an event (HR, 1.546; 95% CI, 1.103 – 2.166) and had a higher risk of death (HR, 1.574; 95% CI, 1.095 – 2.262), compared to patients with a duration of induction chemotherapy &lt; 150 days. Patients with delays during the induction chemotherapy also experienced a significant delay between VIDE 6 and surgery (36 vs. 27 days, p &lt; 0.001) and were treated significantly more often at smaller low-volume centers (63% vs. 48%, p = 0.005). Patients with a prolonged interval &gt; 21 days between surgery and day one of postoperative chemotherapy were at a higher risk to develop an event (HR, 1.406; 95% CI, 1.011 – 1.955), and also had a significantly higher rate of postoperative complications (26% vs. 11%, p &lt; 0.001), compared to patients with a shorter interval. Conclusions: Delays between induction chemotherapy and surgery and between surgery and consolidation chemotherapy are independently associated with a poor outcome in patients with localized EWS. Our results also underscore the need to treat EWS patients in larger and experienced sarcoma centers. The implementation of new and standardized methods in the operative strategy and optimized supportive care during systemic therapy are required to reduce perioperative morbidity and treatment delays.