Trunk Soft Tissue Sarcoma Research Articles

Oncology

The October 2024 Oncology Roundup360 looks at: Composite reconstruction: is it the answer for pelvic resections?; Can the cartilaginous thickness determine the risk of malignancy in pelvic cartilaginous tumours, and how accurate is the preoperative biopsy of these tumours?; Incidence and survival outcomes of patients with high-grade appendicular bone sarcoma and isolated regional lymph node metastasis; Improved metastatic-free survival after systematic re-excision following complete macroscopic unplanned excision of limb or trunk soft-tissue sarcoma; UK guidelines for the management of soft-tissue sarcomas; Current management of desmoid tumours: a review.

27 Long-Term Outcomes of Extremity and Trunk Soft Tissue Sarcoma Using Preoperative Radiation and Conservative Surgery

27 Long-Term Outcomes of Extremity and Trunk Soft Tissue Sarcoma Using Preoperative Radiation and Conservative Surgery

1730P Preliminary results of phase II study on preoperative intensity-modulated radiotherapy with concurrent PARP inhibitor for patients with non-metastatic inoperable or borderline operable extremity and trunk soft tissue sarcoma

1730P Preliminary results of phase II study on preoperative intensity-modulated radiotherapy with concurrent PARP inhibitor for patients with non-metastatic inoperable or borderline operable extremity and trunk soft tissue sarcoma

The role of free flap reconstruction after resection of extremity and trunk soft tissue sarcomas. Results of two referral centers in Argentina

IntroductionFor patients affected by extremity or trunk soft-tissue sarcomas (STS) large resections might be needed to achieve negative margins. This is a common scenario especially in locally advanced or recurrent tumors often within a pre-irradiated field. The objective of this study was to evaluate the results of free-flap reconstructions (FFR) after sarcoma surgery. ObjectiveThe endpoints were surgical results, quality of surgical margins and oncological outcome. MethodsRetrospective analysis of patients with extremity and trunk STS with free-flap reconstruction between 2008 and 2022. Demographic and tumor data, perioperative treatment, margin status, morbidity and evolution were evaluated. ResultsOf 467 patients, 25 (5.35%) required 26 free-flap reconstructions. Surgery was performed on an irradiated field in 8 (32%) patients. Reconstructions were mostly needed for distal lower extremity resections and the most common type of flap used was antero-lateral tight (ALT) flap. No R2 resections were performed. R0 and R1 resections were achieved in 22 (84.6%) and 4 (15.4%), respectively. All R1 resections were preplanned positive along a preserved critical structure. Surgical morbidity rate was 26% (7/26) and the re-operation rate was 15% (4/26) with 7.7% flap losses (2/26). At a median follow-up of 38 months, 7 (28%) patients presented local recurrences. ConclusionIn a referral sarcoma center, having a multidisciplinary surgical team capable of complex resections and reconstructions is of utmost importance for a correct and integral surgical planning. This allows optimal oncologic resections with acceptable morbidity.

Outcomes and complications of postoperative seroma cavities following soft-tissue sarcoma resection.

Seroma development is a known complication following extremity and trunk soft-tissue sarcoma (STS) resection. The purpose of this study is to evaluate and characterize seroma outcomes and the development of associated complications. A retrospective review of 123 patients who developed postoperative seromas following STS resection at a single institution was performed. Various patient and surgical factors were analyzed to determine their effect on overall seroma outcomes. 77/123 seromas (62.6%) were uncomplicated, 30/123 (24.4%) developed infection, and 16/123 (13.0%) were symptomatic and required aspiration or drainage for symptom relief at an average of 12.2 months postoperatively. 65/123 (52.8%) seromas resolved spontaneously at an average time of 12.41 months. Seromas in the lower extremity (p=0.028), surgical resection volume >864 cm3, (p=<0.001) and initial seroma volume >42 cm3 (p=<0.001) increased the likelihood of infection. 90% of infected seromas developed the infection within the first three months following initial resection. No seromas which were aspirated or drained ultimately developed an infection following these procedures, though 50% recurred. Most seromas following STS resection are uncomplicated and do not require intervention, though a large resection cavity >864 cm3 and a large seroma volume >42 cm3 are risk factors for complications.

Unplanned excision of extremity and superficial trunk soft tissue sarcomas

Unplanned excision of extremity and superficial trunk soft tissue sarcomas

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.

Predicting five-year mortality in soft-tissue sarcoma patients.

The aim of this study was to identify factors associated with five-year cancer-related mortality in patients with limb and trunk soft-tissue sarcoma (STS) and develop and validate machine learning algorithms in order to predict five-year cancer-related mortality in these patients. Demographic, clinicopathological, and treatment variables of limb and trunk STS patients in the Surveillance, Epidemiology, and End Results Program (SEER) database from 2004 to 2017 were analyzed. Multivariable logistic regression was used to determine factors significantly associated with five-year cancer-related mortality. Various machine learning models were developed and compared using area under the curve (AUC), calibration, and decision curve analysis. The model that performed best on the SEER testing data was further assessed to determine the variables most important in its predictive capacity. This model was externally validated using our institutional dataset. A total of 13,646 patients with STS from the SEER database were included, of whom 35.9% experienced five-year cancer-related mortality. The random forest model performed the best overall and identified tumour size as the most important variable when predicting mortality in patients with STS, followed by M stage, histological subtype, age, and surgical excision. Each variable was significant in logistic regression. External validation yielded an AUC of 0.752. This study identified clinically important variables associated with five-year cancer-related mortality in patients with limb and trunk STS, and developed a predictive model that demonstrated good accuracy and predictability. Orthopaedic oncologists may use these findings to further risk-stratify their patients and recommend an optimal course of treatment.

L’indice de comorbidité de Charlson ajusté selon l’âge est un outil pronostique précieux dans le sarcome des tissus mous opérable du tronc et des extrémités

BackgroundAdvanced age and presence of comorbidities affect prognosis and treatment decisions in patients with soft tissue sarcoma (STS). However, coeffect of age and comorbidities is still unknown. We aimed to investigate prognostic value of age-adjusted Charlson Comorbidity Index (ACCI) in trunk and extremity STS operated with curative intent. HypothesisPreoperative ACCI might predict survival outcomes independently in patients with STS of trunk and extremities. Patients and methodsThe study included 151 patients and ACCI was calculated for each patient. We categorized the patients into two groups according to median ACCI. We retrospectively collected data about clinicopathologic and treatment-related factors, and evaluated potential prognostic factors for disease-free survival (DFS) and overall survival (OS) using univariate and multivariate analyses. ResultsMedian age was 50 (18–86) years. There were 89 male and 62 female patients. Lower extremities were the most common tumor sites (73.5 %). Most of the patients had high grade tumors (84.1 %) and stage 3 disease (66.9 %). Radiotherapy and chemotherapy were carried out in 106 and 58 patients, respectively. Overall prevalence of comorbidity was 29.1 %. Median ACCI was 3 (2–9). Older age (p<0.001), worse performance status (p<0.001), larger tumor size (p=0.03), higher grade tumors (p=0.03) and advanced stage (p=0.04) were associated with higher ACCI (≥3). Median follow-up time was 32 months, 50.3 % of patients had disease recurrence, and 35.8 % died. Median DFS (p=0.001) and OS (p=0.001) of patients with low ACCI (<3) were significantly longer than patients with high ACCI. Multivariate analysis determined ACCI as an independent prognostic indicator for both DFS (HR 1.72, p=0.02) and OS (HR 2.02, p=0.04). DiscussionACCI is a valuable prognostic tool to be used in the preoperative setting of patients with STS. Higher ACCI was found to be independently associated with worse survival outcomes. For each patient with STS, evaluating comorbidities and combining them with age appears to be a critical step in modifying therapy options. Level of evidenceIV, retrospective observational study.

ASO Visual Abstract: Practice Pattern Variability in the Management of Regional Lymph Node Metastasis in Extremity and Trunk Soft Tissue Sarcoma (ETSTS): A Survey of the Society of Surgical Oncology (SSO) and Musculoskeletal Tumor Society (MSTS) Membership.

ASO Visual Abstract: Practice Pattern Variability in the Management of Regional Lymph Node Metastasis in Extremity and Trunk Soft Tissue Sarcoma (ETSTS): A Survey of the Society of Surgical Oncology (SSO) and Musculoskeletal Tumor Society (MSTS) Membership.

Practice Pattern Variability in the Management of Regional Lymph Node Metastasis in Extremity and Trunk Soft Tissue Sarcoma: A Survey of the Society of Surgical Oncology and Musculoskeletal Tumor Society Membership.

Regional lymph node metastasis in extremity and trunk soft tissue sarcoma (ETSTS) is rare with no standardized management. We sought to determine management patterns for regional lymph node metastasis in ETSTS. A survey regarding the management of ETSTS lymph node metastasis was distributed to the membership of the Musculoskeletal Tumor Society (MSTS) and the Society of Surgical Oncology (SSO) in January 2022. The survey queried the type of training (surgical oncology, orthopedic oncology), details of their practice setting, and management decisions of hypothetical ETSTS scenarios that involved potential or confirmed lymph node metastasis. The survey was distributed to 349 MSTS members (open rate of 63%, completion rate 21%) and 3026 SSO members (open rate of 55%, completion rate 4.7%) and was completed by 214 respondents, of whom 73 (34.1%) and 141 (65.9%) were orthopedic oncology and surgical oncology fellowship-trained, respectively. The majority of respondents practiced in an academic setting (n=171, 79.9%) and treat >10 extremity sarcoma cases annually (n=138, 62.2%). In scenarios with confirmed nodal disease for clear cell and epithelioid sarcoma, surgical oncologists were inclined to perform lymphadenectomy, while orthopedic oncologists were inclined to offer targeted lymph node excision with adjuvant radiation (p<0.001). There was heterogeneity of responses regarding the management of nodal disease regardless of training background. Self-reported management of nodal disease in ETSTS was variable among respondent groups with differences and similarities based on training background. These data highlight the variability of practice for nodal disease management and the need for consensus-based guidelines.

Impact of the coronavirus disease 2019 pandemic on sarcoma management in France: a 2019 and 2020 comparison.

The coronavirus disease 2019 (COVID-19) pandemic was an unprecedented shock to the healthcare systems, and its consequences on managing rare cancers are unknown. We investigated COVID-19's impact on the activity of sarcoma-labeled networks by comparing key indicators in 2019-2020 (before and during the pandemic, respectively). We compared the incidence of limb and trunk soft tissue sarcomas, surgery rate, surgery center, surgery quality, and surgery delays nationally and in various regions, focusing on the three most severely affected regions. In this study, sarcoma incidence did not decrease, and the tumor and patient characteristics were similar in both years. The number of patients who underwent surgery in the labeled centers increased significantly (63% versus 57%, p = 0.015), the rate of R0 resection increased (55% versus 47%, p = 0.004), and the rate of re-excision decreased (12% versus 21%, p < 0.0001). In the univariate analysis, the time to surgery was similar in both years. Cox regression analysis revealed that the factors associated with a longer time to surgery were age > 70 years (p = 0.003), retroperitoneal location (p > 0.001), tumor size (p < 0.001), deep tumors (p < 0.001), and regions (p < 0.001). However, we have observed an increase in the time before surgery in the regions most stroked by the COVID-19 pandemic. The model of the labeled center network for managing rare tumors was resilient. Paradoxically, the quality indicators improved during the pandemic due to the direct referral of patients with sarcomas to the labeled centers. This study shows that a nationwide network organization has made it possible to maintain care for these rare tumors during the pandemic.

Arterial Reconstruction for En-Bloc Resection of Soft Tissue Sarcoma: A Single Tertiary Center Experience

Tertiary centers recruit a number of locally advanced or recurrent soft tissue sarcomas (STSs) that require large tissue loss including vessels. Arterial reconstruction (AR) in the context of patients with cancer who may receive radiotherapy (RT) and chemotherapy (CT) is challenging. This retrospective single centre cohort study includes patients affected by extremities or trunk STS who underwent an AR during sarcoma resection, between October 2015 and February 2021 at Institut Curie. The endpoints of this study were to analyze the morbidity, the patency, and the impact on surgical margins of such associations. Of 976 patients operated, 21 (2.15%) had AR. Seventeen (81%) had American Society of Anesthesiologists (ASA) scores ≥2. Locations were as follows: intra-abdominal n=9 (43%), lower limb n=8 (38%), upper limb n=3 (14%), and cervical n=1 (5%). N=11 (52.3%) and n=5 (23.8%) received RT or were operated on a preirradiated field, respectively. N=7 (34%) patients received CT. Vein graft was used in n=12 (57%). Musculo-cutaneous flaps were associated in n=13 (62%) patients. Margins of resection were R0 n=19 (90.4%), R1 n=2, and R2 n=0. The median follow-up was 16months [6-44]. No postoperative death occurred. Two patients died of metastasis. At 1, 6, 12, and 24months the primary patency was 80.9%, 71.4%, 87.5%, and 88.9%, respectively. Seven patients (33%) presented perioperative infection. Reoperation rate at 1, 6, and 12months were 38%, 14%, and 5%, respectively. Ten patients (48%) presented persistent lymphoedema during follow-up. AR enlarges the possibilities of STS excision with healthy margins and achieves good patency. Majority of patients were ASA ≥ 2 and received adjuvant treatments. In this particular context, morbidity is high and requires an upfront multidisciplinary management taking into account all these specific issues.

Clinical reliability of pedicled perforator flaps in the management of adult limb and trunk soft tissue sarcomas: Experience of two French expert centres.

Limb-sparing surgery combined with radiation has become the standard treatment for soft tissue sarcomas. Despite the many advantages of reconstruction procedures, such as muscle-sparing flap and local reconstruction, the use of pedicled perforator flaps remains non-consensual due to doubts about their reliability when associated with radiotherapy. This study evaluated their surgical reliability in reconstructive surgery for limb and trunk soft tissue sarcomas, in terms of healing time, wound disorders, and postoperative complications, regardless of radiation timing. We realized a retrospective, observational, bi-center study (Cancer University Institute of Toulouse Oncopole, France and Bergonié Institute Bordeaux, France) and describes pedicled perforator flaps performed between January 2015 and January 2021. A total of 74 flaps were included. The median age of the population was 70-year-old. The group consisted of 68.8% (n=51/74) propeller flaps. We found a partial necrosis rate of 28.4% (n=21/74), scar disunion of 48.6% (n=36/74), local infection of 10.8% (n=8/74), and venous congestion of 13.5% (n=10/74). Only 16.2% (n=12/74) required secondary surgical repair to a local complication. The average length of stay was 7.3 days [1.0-25.0]. The mean operating time of our flaps was 133.4min [38.0-280.0]. Pedicled perforator flaps are a surgical technique that can be used in reconstructive surgery for limb and trunk soft tissue sarcomas in adults, regardless of radiation timing. However, these flaps carry a high rate of postoperative complications so they should be reserved for expert surgeons in referral centers.

Age-adjusted Charlson Comorbidity Index is a valuable prognostic tool in operable soft tissue sarcoma of trunk and extremities

BackgroundAdvanced age and presence of comorbidities affect prognosis and treatment decisions in patients with soft tissue sarcoma (STS). However, coeffect of age and comorbidities is still unknown. We aimed to investigate prognostic value of age-adjusted Charlson Comorbidity Index (ACCI) in trunk and extremity STS operated with curative intent. HypothesisPreoperative ACCI might predict survival outcomes independently in patients with STS of trunk and extremities. Patients and methodsThe study included 151 patients and ACCI was calculated for each patient. We categorized the patients into two groups according to median ACCI. We retrospectively collected data about clinicopathologic and treatment-related factors, and evaluated potential prognostic factors for disease-free survival (DFS) and overall survival (OS) using univariate and multivariate analyses. ResultsMedian age was 50 (18–86) years. There were 89 male and 62 female patients. Lower extremities were the most common tumor sites (73.5%). Most of the patients had high grade tumors (84.1%) and stage 3 disease (66.9%). Radiotherapy and chemotherapy were carried out in 106 and 58 patients, respectively. Overall prevalence of comorbidity was 29.1%. Median ACCI was 3 (2-9). Older age (p<0.001), worse performance status (p<0.001), larger tumor size (p=0.03), higher grade tumors (p=0.03) and advanced stage (p=0.04) were associated with higher ACCI (≥3). Median follow-up time was 32 months, 50.3% of patients had disease recurrence, and 35.8% died. Median DFS (p=0.001) and OS (p=0.001) of patients with low ACCI (<3) were significantly longer than patients with high ACCI. Multivariate analysis determined ACCI as an independent prognostic indicator for both DFS (HR 1.72, p=0.02) and OS (HR 2.02, p=0.04). DiscussionACCI is a valuable prognostic tool to be used in the preoperative setting of patients with STS. Higher ACCI was found to be independently associated with worse survival outcomes. For each patient with STS, evaluating comorbidities and combining them with age appears to be a critical step in modifying therapy options. Level of evidenceIV, retrospective observational study.

Preliminary Results of Phase II Study on Preoperative Intensity-Modulated Radiotherapy with Concurrent Tyrosine Kinase Inhibitor for Patients with Non-Metastatic Extremity and Trunk Soft Tissue Sarcoma

<h3>Purpose/Objective(s)</h3> Preoperative radiotherapy (RT) is one of the recommended treatments for primary extremity and trunk soft tissue sarcoma, however, the pathological remission is relatively low, and survival is not improved. We hypothesized that the addition of tyrosine kinase inhibitor (TKI) will improve the pathological remission rate without significant increase of major wound complications (MWCs). <h3>Materials/Methods</h3> Two phase II study were initiated in our center. Primary or recurrent non-metastatic extremity or trunk soft tissue sarcoma was enrolled. Patients received preoperative intensity-modulated radiotherapy (IMRT) of 50Gy in 25 fractions with concurrent and sequential Anlotinib (12 mg QD for 2 weeks, 3 cycles in total) or Apatinib (500 mg QD, 5 days per week, for 9 weeks in total), followed by wide resection. NCI-CTC 5.0, RECIST 1.1 criteria, and EORTC-STBSG criteria was used to evaluate acute toxicities, clinical response and pathological grading. The primary endpoint was defined as MWCs as per the SR2 criteria within 4 months post-surgery. <h3>Results</h3> From Jul 2020 to Dec 2021, 31 patients were enrolled and completed RT. The median onset age is 55 (22-82) years old. There are 26 and 5 patients with primary untreated and locally relapsed disease, respectively. The median tumor size is 10.5 (3.7-19.5) cm, with 23 patients (74.2%) larger than 8cm. Twenty-seven tumors (87.1%) were evaluated as unresectable or borderline resectable, which was defined as impossible or difficult to conserve limb with non-R2 wide resection. There were 21, 9 and 1 patients having Anlotinib, Apatinib and none, respectively. All except 5 took TKI as per protocol, with 4 patients having dose reduction due to Grade 3 toxicities. The observed ≥Grade 3 toxicities are: hypertension in 4 patients (19.1%) in Anlotinib group and 2 patients (22.2%) in Apatinib group, and one Grade 4 hepatotoxicity in Apatinib group (11.1%). There are 14 (14/30, 46.7%) and 16 patients (16/30, 53.3%) who achieved partial response (PR) and SD as per RECIST 1.1 criteria at 1-month post-radiotherapy, respectively. All the patients who had PR had obvious tumor shrink at the first 1 to 2 weeks during radiotherapy. Six out of 24 patients (25%) who underwent wide resection with at least 6 weeks follow-up had MWCs, with all in lower extremity. There were 4 (4/26, 15.4%), 3 (3/26, 11.5%) and 3 (3/26, 11.5%) patients achieving pathological Grade A, B, and C remission as per EORTC-STBSG criteria, respectively. All the 22 patients with unresectable or borderline resectable tumor had non-R2 limb-conserving wide resection, with 18 R0 and only 4 R1 resection. <h3>Conclusion</h3> For patients with non-metastatic extremity or trunk primary sarcoma, the combination of TKI and pre-operative RT is safe and well-tolerated, and achieve favorable clinical and pathological response. The earlier response with addition of TKI made more patients with unresectable or borderline resectable tumor completely resected by limb-conserving wide resection. NCT05167994, NCT05235100

Refining the Approach to Patients with Primary Soft Tissue Sarcoma of the Extremities and Trunk Wall: Outcome Improvement Over Time at a Single Institution.

The improved outcome of extremity soft tissue sarcoma patients surgically treated until 2007 at the authors' institution was previously reported. This study updates the analysis at a later follow-up and extends the patients'cohort to assess changes in outcomes over time for extremity and superficial trunk soft tissue sarcoma (ESTSTS) treated at a single referral center. All consecutive patients with primary localized adult-type ESTSTSsurgically treated at the authors' institution between 1987 and 2017 wereincluded and divided into group 1 (1987-2002) and group 2 (2003-2017) according to primary surgery year. Crude cumulative incidence (CCI) of sarcoma-specific mortality (SSM), local recurrence (LR), and distant metastases (DM)were calculated in a competing-risks framework. DM-free survival (DMFS) and post-DM survivalwere also assessed. The study identified 2382 patients. The median follow-up was 104 months (range, 63-127 months), and the post-DM follow-up was 76 months (range, 37-126 months). Since 2003, an increased adoption of preoperative treatments was observed: the use ofchemotherapy, radiotherapy and combined chemoradiotherapy went from 10.5% to 23.7%, from 1.7% to 17.8%, and from 1% to 11.8%respectively. This change in treatment strategies was associated to an improvementin CCI-SSM (27.8% vs 19.5%; P < 0.001), CCI-LR (14.1 vs 7.5%; P < 0.001), DMFS (57.9% vs 65.8%; P = 0.004), and post-DM (12.2% vs 20.1%; P = 0.012), but not in CCI-DM. Increased adoption of preoperative treatments and greater availability of medical agents in the recent years were associated to better outcomes. New treatments are eagerly awaited for further improvement of outcome for ESTSTS patients because no major changes have been observed since 2003.

Preoperative Radiation for Soft Tissue Sarcomas: How Much Is Needed?

Preoperative radiation therapy is an important component of curative treatment for extremity and superficial trunk soft tissue sarcomas. It has traditionally been delivered to a dose of 50 Gy in 2 Gy fractions over 5 weeks. With significant advances in the multidisciplinary approach to soft tissue sarcomas, preoperative radiation therapy may be omitted for certain cases, delivered over a shortened period of time (1-3 weeks), deintensified for myxoid liposarcomas, or combined with systemic therapy to improve the therapeutic ratio. This article reviews the innovative preoperative radiation therapy strategies currently used to treat extremity and superficial trunk soft tissue sarcomas.

The role of Ifosfamide–doxorubicin chemotherapy in histology-specific, high grade, locally advanced soft tissue sarcoma, a 14-year experience

PurposeTo compare long-term outcomes of high-grade, primary soft-tissue-sarcoma (STS), using Ifosfamide–Doxorubicin vs local therapy alone, in histology-specific sarcomas. MethodsRetrospective analysis was performed on 127 patients from 2005 to 2018, with high-grade STS of extremity or trunk, >5 cm, that were either Synovial-Cell, Dedifferentiated-Liposarcoma (DDL), Myxofibrosarcoma, Round-Cell-Liposarcoma (RCLS), Undifferentiated-Pleomorphic-Sarcoma (UPS), or Undifferentiated-Sarcoma-not-otherwise-specified (US-NOS), with central pathology review. Ifosfamide–Doxorubicin was generally given neoadjuvant over 5 cycles, followed by radiation and wide excision, with chemotherapy given in 38 patients, while 89 received local therapy alone. Multi-variable-analysis (MVA) of prognostic factors was performed, and local-recurrence-free-survival (LRFS), distant-metastases-free-survival (DMFS), disease-specific-survival (DSS), and overall-survival (OS) were estimated using Kaplan–Meier, and adjusted using propensity-score matching. ResultsMedian follow-up was 4.5 years. Younger age (p < 0.0001) and Synovial histology (p = 0.0002) were more likely to undergo chemotherapy. Ifosfamide–Doxorubicin improved 5-year DMFS (p = 0.02), DSS (p = 0.01), and OS (p = 0.01), by univariate comparisons, as well as sub-analysis of non-synovial histology, but significance was lost after propensity-score matching for DMFS (p = 0.10), DSS (p = 0.09), and OS (p = 0.07). Size >10 cm, trunk location, and lack of chemotherapy significantly lowered DMFS, DSS, and OS on MVA, while DDL had more favorable survival; although size, trunk location, and DDL histology were not significantly different between treatment groups. Ifosfamide–Doxorubicin independently improved DMFS (p = 0.001), DSS (p = 0.01), and OS (p = 0.001) on MVA. ConclusionIfosfamide–Doxorubicin may be more beneficial in younger patients with >5 cm, high-grade, STS of the trunk or extremity in Synovial-Cell, DDL, Myxofibrosarcoma, RCLS, UPS, and US-NOS.

Evaluating Thresholds to Adopt Hypofractionated Preoperative Radiotherapy as Standard of Care in Sarcoma.

Introduction Data supporting hypofractionated preoperative radiation therapy (RT) for patients with extremity and trunk soft tissue sarcoma (STS) are currently limited to phase II single-institution studies. We sought to understand the type and thresholds of clinical evidence required for experts to adopt hypofractionated RT as a standard-of-care option for patients with STS. Methods An electronic survey was distributed to multidisciplinary sarcoma experts. The survey queried whether data from a theoretical, multi-institutional, phase II study of 5-fraction preoperative RT could change practice. Using endpoints from RTOG 0630 as a reference, the survey also queried thresholds for acceptable local control, wound complication, and late toxicity for the study protocol to be accepted as a standard-of-care option. Responses were logged from 8/27/2020 to 9/8/2020 and summarized graphically. Results The survey response rate was 55.3% (47/85). Local control is the most important clinical outcome for sarcoma specialists when evaluating whether an RT regimen should be considered standard of care. 17% (8/47) of providers require randomized phase III evidence to consider hypofractionated preoperative RT as a standard-of-care option, whereas 10.6% (5/47) of providers already view this as a standard-of-care option. Of providers willing to change practice based on phase II data, most (78%, 29/37) would accept local control rates equivalent to or less than those in RTOG 0630, as long as the rate was higher than 85%. However, 51.3% (19/37) would require wound complication rates superior to those reported in RTOG 0630, and 46% (17/37) of respondents would accept late toxicity rates inferior to RTOG 0630. Conclusion Consensus building is needed among clinicians regarding the type and threshold of evidence needed to evaluate hypofractionated RT as a standard-of-care option. A collaborative consortium-based approach may be the most pragmatic means for developing consensus protocols and pooling data to gradually introduce hypofractionated preoperative RT into routine practice.