Extremity Soft Tissue Sarcoma Research Articles

Neoadjuvant Radiotherapy Is Associated with Fewer Acute Adverse Skin Reactions Without Increased Risk of Postoperative Wound Complications in High-Grade Extremity Soft Tissue Sarcoma - A Retrospective Comparative Study with A Mean Follow-Up of 7 Years

Aim: In this study, we aim to compare the adverse effects and oncological outcomes of patients with high-grade extremity soft tissue sarcoma receiving neoadjuvant or adjuvant RT. Methods: From 2008 to 2022, Sixty-four patients underwent limb-preserving surgery in our institute for localized high-grade extremity soft tissue sarcoma were included. Thirty-nine patients received adjuvant radiotherapy while twenty-five patients received neoadjuvant RT before surgery if the soft tissue sarcomas were close to the neurovascular bundles, bones or histological types of myxoid liposarcoma or rhabdomyosarcoma. Primary outcomes were acute RT-related skin adverse reactions and significant side effects comprising postoperative wound complications, pathological fractures and RT-induced sarcoma. Secondary outcomes included surgical margin quality, Local-Recurrence (LR)-free survival, metastasis-free survival and overall survivorship. Results and Discussion: Patients in the neoadjuvant RT group had significantly fewer acute RT-induced adverse skin reactions than the adjuvant RT group (p=0.044, Table 2). None in the neoadjuvant RT group suffered severe acute skin reaction (RTOG grade 3-4). Wound infection (n=2) and pathological fracture (n=1) were rare in both adjuvant and neoadjuvant RT groups (P=0.640 & 1.000 respectively). Survival curves for local-recurrence-free survival, metastasis-free survival and overall survivorship of both neoadjuvant and adjuvant groups were analyzed via Kaplan-Meier Curve. All results are statistically insignificant, with p=0.835, 0.948 and 0.540, respectively. Presence of metastasis was the only statistically significant predictor of the overall survival-adjusted hazard ratio of 8.7 (95%CI 2.7-28), p<0.001. Conclusion: Patients with neoadjuvant RT had lower cumulative radiation doses and fewer acute adverse skin reactions. There was no increased risk of postoperative wound complication compared to adjuvant RT. The LR-free survival, metastasis-free survival and overall survival were comparable in both groups. Our results suggested that postponing surgery to eight weeks after neoadjuvant RT and primary wound closure were associated with fewer wound complications, but further studies were warranted.

Team Approach: Extremity Soft Tissue Sarcoma.

» Synovial sarcoma is a soft tissue sarcoma that most commonly presents in the extremity in a periarticular location.» As the history and physical examination of patients with synovial sarcoma can overlap considerably with those of patients with non-oncologic orthopedic conditions, it is important that orthopedic surgeons maintain a high level of suspicion when caring for patients with extremity masses.» Soft tissue sarcomas are best treated using a team approach. Early recognition and referral to a multidisciplinary sarcoma team are crucial to ensure the best clinical outcome for the patient.

Management of tumor volume changes during preoperative radiotherapy for extremity soft tissue sarcoma: a new strategy of adaptive radiotherapy.

Using adaptive radiotherapy (ART), to determine objective clinical criteria that identify extremity soft tissue sarcoma (ESTS) patients requiring adaptation of their preoperative radiotherapy (RT) plan. We included 17 patients with a lower extremity ESTS treated between 2019 and 2021 with preoperative RT, using helicoidal intensity-modulated RT (IMRT) tomotherapy, before surgical resection. We collected clinical, tumor parameters and treatment data. Repositioning was ascertained by daily Megavoltage computed tomography (MVCT) imaging. Using the PreciseART technology we retrospectively manually delineated at least one MVCT for each patient per week and recorded volume and dosimetric parameters. A greater than 5% change between target volume and planned target volume (PTV) dosimetric coverage from the initial planning CT scan to at least one MVCT was defined as clinically significant. All 17 patients experienced significant tumor volume changes during treatment; 7 tumors grew (41%) and 10 shrank (59%). Three patients (18%), all undifferentiated pleomorphic sarcomas (UPS) with increased volume changes, experienced significant reductions in tumor dose coverage. Seven patients required a plan adaptation, as determined by practical criteria applied in our departmental practice. Among these patients, only one ultimately experienced a significant change in PTV coverage. Three patients had a PTV decrease of coverage. Among them, 2 did not receive plan adaptation according our criteria. None of the patients with decreased tumor volumes had reduced target volume coverage. Monitoring volume variations by estimating gross tumor volume (GTV) on MVCT, in addition to axial and sagittal linear tumor dimensions, appeared to be most effective for detecting reductions in PTV coverage throughout treatment. Variations in ESTS volume are evident during preoperative RT, but significant dosimetric variations are rare. Specific attention should be paid to grade 2-3 UPSs during the first 2 weeks of treatment. In the absence of dedicated software in routine clinical practice, monitoring of tumor volume changes by estimating GTV may represent a useful strategy for identifying patients whose treatment needs to be replanned.

Emerging innovations and advancements in the treatment of extremity and truncal soft tissue sarcomas.

In this special edition update on soft tissue sarcomas (STS), we cover classifications, emerging technologies, prognostic tools, radiation schemas, and treatment disparities in extremity and truncal STS. We discuss the importance of enhancing local control and reducing complications, including the role of innovative imaging, surgical guidance, and hypofractionated radiation. We review advancements in systemic and immunotherapeutic treatments and introduce disparities seen in this vulnerable population that must be considered to improve overall patient care.

Calculating Tumor Volume Using Three-Dimensional Models in Preoperative Soft-Tissue Sarcoma Surgical Planning: Does Size Matter?

This feasibility study aims to explore the use of three-dimensional virtual surgical planning to preoperatively determine the need for reconstructive surgery following resection of an extremity soft-tissue sarcoma. As flap reconstruction is performed more often in advanced disease, we hypothesized that tumor volume would be larger in the group of patients that had undergone flap reconstruction. All patients that were treated by surgical resection for an extremity soft-tissue sarcoma between 1 January 2016 and 1 October 2019 in the University Medical Center Groningen were included retrospectively. Three-dimensional models were created using the diagnostic magnetic resonance scan. Tumor volume was calculated for all patients. Three-dimensional tumor volume was 107.8 (349.1) mL in the group of patients that had undergone primary closure and 29.4 (47.4) mL in the group of patients in which a flap reconstruction was performed, p = 0.004. Three-dimensional tumor volume was 76.1 (295.3) mL in the group of patients with a complication following ESTS treatment, versus 57.0 (132.4) mL in patients with an uncomplicated course following ESTS treatment, p = 0.311. Patients who had undergone flap reconstruction had smaller tumor volumes compared to those in the group of patients treated by primary closure. Furthermore, a larger tumor volume did not result in complications for patients undergoing ESTS treatment. Therefore, tumor volume does not seem to influence the need for reconstruction. Despite the capability of three-dimensional virtual surgical planning to measure tumor volume, we do not recommend its utilization in the multidisciplinary extremity soft-tissue sarcoma treatment, considering the findings of the study.

Preoperative radiation therapy increases adherence in patients with high-risk extremity soft tissue sarcoma

BackgroundSurgery and radiation therapy remain the standard of care for patients with high-grade extremity soft tissue sarcoma that are >5 cm. Radiation therapy is time and labor-intensive for patients, and social determinants of health may affect adherence. The aim of this study was to define demographic, clinical, and treatment factors associated with the completion of radiation therapy and determine if preoperative radiation therapy improved adherence compared to postoperative radiation therapy. MethodsThe cohort included patients in the National Cancer Database with high-grade extremity soft tissue sarcoma >5 cm without nodal or distant metastases who received limb-sparing surgery and radiation therapy with microscopically negative R0 margins. Multivariable logistic regression analyses identified factors associated with radiation therapy sequencing and adherence (defined as completion of 50 Gy preoperative radiation therapy or at least 60 Gy postoperative radiation therapy). A multivariable Cox Proportional Hazards model assessed overall survival. ResultsAmong 2,145 patients, 47.1% received preoperative radiation therapy (n = 1,010), and 52.9% (n = 1135) received postoperative radiation therapy. A greater proportion of patients treated with preoperative (77.2%) versus postoperative radiation therapy (64.9%, P < .0001) received the recommended dose. More patients with private insurance (49.8% vs 35.3% Medicaid vs 44.9% Medicare, P = .011) and patients treated at an academic medical center (52.6% vs 47.4%, P < .001) received preoperative radiation therapy. Patients who received preoperative radiation therapy had lower odds of receiving insufficient doses of radiation therapy (odds ratio 0.34 [95% CI 0.27–0.47]). Neither radiation therapy adherence nor sequencing were independent predictors of overall survival. ConclusionsPatients who received preoperative radiation therapy were more likely to complete therapy and receive an optimal dose than patients treated with postoperative radiation therapy. Preoperative radiation therapy improves adherence and should be widely considered in patients with high-grade extremity soft tissue sarcoma, particularly in patients at risk for not completing therapy.

The efficacy and safety of direct oral anticoagulants compared with low-molecular-weight heparin for venous thromboembolism prophylaxis after surgical resection of primary lower extremity bone or soft-tissue sarcoma.

The incidence of postoperative venous thromboembolism (VTE)and wound complications is greater after sarcoma resection. We sought to identify differences in postoperative VTE and bleeding complications with direct oral anticoagulants (DOACs)versus low-molecular-weight heparin (LMWH)following resection of lower extremity primary bone or soft tissue sarcoma. We retrospectively identified 2083 patients from the PearlDiver database who underwent resection of primary bone or soft tissue sarcoma of the lower extremity from January 2010 to October 2021 and prescribed LMWH or DOAC within 90-days postoperatively. The primary outcomes were comparison of postoperative incidence and odds of deep venous thrombosis(DVT), pulmonary embolism(PE), and bleeding complications within 90-days following resection. Patients prescribed DOACs had a greater odds of DVT (odds ratio [OR]: 1.60; 95% confidence interval [CI]: 1.06-2.41;p = 0.024) and PE (OR: 3.38;95% CI: 1.96-5.86;p < 0.001) within 90-days following resection of bone sarcoma when compared withthe LMWH cohort. Patients undergoing resection of soft tissue sarcomas also had greater odds DVT (OR: 1.65;95% CI: 1.09-2.49;p = 0.016) and PE (OR: 2.62;95% CI: 1.52-4.54;p < 0.001) in the DOAC cohort. There was no difference in the odds of bleeding complications. This study demonstrated an increased incidence and odds of VTE, but not bleeding complications, when using DOACs versus LMWH after primary bone or soft tissue sarcoma resection. Level III.

Pleomorphic liposarcoma of the extremity with solitary huge liver metastasis at initial diagnosis treated with conversion surgery combined with adjuvant chemotherapy: a case report

BackgroundPleomorphic liposarcoma is the rarest subtype of liposarcoma. Pleomorphic liposarcomas are generally unresponsive to chemotherapy and radiotherapy. Moreover, metastasis in the liver, as the first and sole site, from a primary extremity soft tissue sarcoma, including pleomorphic liposarcoma, is extremely rare. Information regarding the appropriate management of these lesions is limited.Case presentationA 50-year-old Japanese woman presented with a mass in the left thigh. Imaging examination revealed a soft tissue sarcoma on the left posterior thigh. The tumor was histologically diagnosed as pleomorphic liposarcoma. Computed tomography examination for assessment of metastases incidentally detected a huge liver mass. Wide excision of sarcoma was performed prior to chemotherapy. Right trisectionectomy was necessary to achieve hepatic clearance; however, the future liver remnant volume was insufficient. Therefore, we decided to administer anthracycline-based chemotheraphy to shrink the tumor. After seven courses of adriamycin-based chemotherapy, the liver tumor size was reduced from 211 mm × 106 mm × 180 mm to 105 mm × 66 mm × 90 mm. Finally, a right hemihepatectomy was performed. The patient was continuously monitored and was metastasis or local recurrence free within 5 months after liver surgery.ConclusionChemotherapy is effective in some cases for the treatment of unresectable liver metastases of pleomorphic liposarcoma, and complete resection is possible with conversion surgery. If the patient’s general condition permits, anthracycline-based chemotherapy can be used for the treatment of stage 4 pleomorphic liposarcoma.

(Cost-)effectiveness of an individualised risk prediction tool (PERSARC) on patient’s knowledge and decisional conflict among soft-tissue sarcomas patients: protocol for a parallel cluster randomised trial (the VALUE-PERSARC study)

IntroductionCurrent treatment decision-making in high-grade soft-tissue sarcoma (STS) care is not informed by individualised risks for different treatment options and patients’ preferences. Risk prediction tools may provide patients and professionals...

Impact of Surveillance Imaging in Detecting Local and Metastatic Lung Recurrences Among Patients with Sarcomas of the Extremities: A Systematic Review and Meta-analysis.

The surveillance guidelines following treatment completion for patients with high-grade sarcomas of the extremities are based largely upon expert opinions and consensus. In the current meta-analysis, we aim to study the utility of surveillance imaging to diagnose local and metastatic pulmonary relapses among patients with extremity soft tissue sarcomas and primary bone sarcomas. A meta-analysis was performed to assess the sensitivity, specificity and diagnostic odds ratio (DOR) of surveillance imaging to diagnose local and metastatic pulmonary relapse among patients with sarcoma of the extremities. In addition, impact of surveillance imaging on overall survival was assessed. Heterogeneity among eligible studies was evaluated by I2 statistics. Sensitivity analysis was assessed using influence plots and Baujat plots. Ten studies including 2160 patients with sarcoma were found eligible. For diagnoses of local recurrence based on surveillance imaging (nine studies, 1917 patients), the estimated sensitivity, specificity, and DOR were 13.6%, 99.5%, and 78.15, respectively. Only 16.7% of local recurrences were diagnosed based on imaging. For diagnoses of metastatic pulmonary recurrence (eight studies; 1868 patients), estimated sensitivity, specificity, and DOR were 76.1%, 99.3%, and 1059.9, respectively. A sensitivity analysis showed significant heterogeneity among included studies. None of the included studies showed an overall-survival benefit with the use of surveillance imaging. The current meta-analysis challenges the notion of routine use of imaging to detect local relapse, while favoring chest imaging, using either chest radiography or computed tomography scan, for surveillance. Further studies are required to study the ideal surveillance strategy including timing and imaging modality.

Comparison of the incidence of wound complications with preoperative and postoperative radiotherapy in patients with extremity soft tissue sarcoma resection: A meta-analysis.

We performed a meta-analysis to compare the effect of preoperative and postoperative radiotherapy on wound complications after resection of extremity soft tissue sarcoma (ESTS). A comprehensive computerised search of the PubMed, Cochrane Library, Web of Science, EMBASE, China National Knowledge Infrastructure (CNKI), VIP, and Wanfang databases was conducted from their inception to August 2023 to identify studies comparing the effect of preoperative and postoperative radiotherapy on wound complications after ESTS resection. Two investigators independently screened the literature, extracted the data, and assessed the quality of the articles. The meta-analysis was performed using RevMan 5.4 software. Nine studies with 1271 patients were included, with 631 and 640 patients in the preoperative and postoperative radiotherapy groups, respectively. The results showed that the incidence of postoperative wound complications after ESTS resection was significantly higher with preoperative radiotherapy than with postoperative radiotherapy (27.26% vs. 12.03%, odds ratio [OR]: 2.88, 95% confidence interval [CI]: 2.12-3.91, p < 0.001). However, the rate of local recurrence of ESTS was significantly lower with preoperative radiotherapy than with postoperative radiotherapy (8.75% vs. 14.81%, OR: 0.57, 95% CI: 0.36-0.91, p = 0.02), and the 3-year overall survival was significantly higher in the preoperative radiotherapy group than in the postoperative radiotherapy group (82.24% vs. 70.04%, OR: 1.97, 95% CI: 1.05-3.71, p = 0.03). This pooled analysis suggests that although preoperative radiotherapy increases the rate of wound complications in ESTS compared with postoperative radiotherapy, it significantly reduces the rate of local recurrence after ESTS resection and improves the overall survival of patients. Owing to the limitations in the number and quality of the included studies, additional prospective cohort studies or randomised controlled trials are required to confirm these findings.

Effect of radiotherapy on local recurrence, distant metastasis and overall survival in 1200 extremity soft tissue sarcoma patients. Retrospective analysis using IPTW-adjusted models

Background and purposeNeoadjuvant (NRTX) and adjuvant radiotherapy (ARTX) reduce local recurrence (LR) risk in extremity soft tissue sarcoma (eSTS), yet their impact on distant metastasis (DM) and overall survival (OS) is less well defined. This study aimed at analysing the influence of NRTX/ARTX on all three endpoints using a retrospective, multicentre eSTS cohort. Materials and methods1200 patients (mean age: 60.7 ± 16.8 years; 44.4 % females) were retrospectively included, treated with limb sparing surgery and curative intent for localised, high grade (G2/3) eSTS. 194 (16.2 %), 790 (65.8 %), and 216 (18.0 %) patients had received NRTX, ARTX and no RTX, respectively. For the resulting three groups (no RTX vs. NRTX, no RTX vs. ARTX, NRTX vs. ARTX) Fine&Gray models for LR and DM, and Cox-regression models for OS were calculated, with IPTW-modelling adjusting for imbalances between groups. ResultsIn the IPTW-adjusted analysis, NRTX was associated with lower LR-risk in comparison to no RTX (SHR [subhazard ratio]: 0.236; p = 0.003), whilst no impact on DM-risk (p = 0.576) or OS (p = 1.000) was found. IPTW-weighted analysis for no RTX vs. ARTX revealed a significant positive association between ARTX and lower LR-risk (SHR: 0.479, p = 0.003), but again no impact on DM-risk (p = 0.363) or OS (p = 0.534). IPTW-weighted model for NRTX vs. ARTX showed significantly lower LR-risk for NRTX (SHR for ARTX: 3.433; p = 0.003) but no difference regarding DM-risk (p = 1.000) or OS (p = 0.639). ConclusionNRTX and ARTX are associated with lower LR-risk, but do not seem to affect DM-risk or OS. NRTX may be favoured over ARTX as our results indicate better local control rates.

Epidemiology and survival factors of appendicular myxofibrosarcoma: a SEER-retrospective study.

The low incidence of myxofibrosarcoma (MFS) makes high power studies difficult to perform. Demographic and prognostic factors for MFS and how they differ from all extremity soft tissue sarcomas (STS) are not well understood. The purpose of this study was to characterize a large cohort of patients with MFS and evaluate epidemiologic and survival factors when compared to all STS. We performed a retrospective review of the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2015 to identify 1,440 patients diagnosed with MFS and 12,324 with STS. Survival curves were creased using Kaplan-Meier, and Cox regression analyses were performed to identify hazard ratios (HRs). Overall survival was greater for STS than MFS (79% vs. 67%). Patients with MFS had a higher average age at diagnosis than STS (62 vs. 56), and older age was strongly associated with decreased survivorship for MFS (HR = 7.94). A greater proportion of patients under 30 diagnosed with MFS were female when compared to STS (49.6% vs. 45.4%). The incidence of MFS and STS increased over the 15-year period, with MFS increasing at a greater rate than STS (1.25% vs. 2.59%). Survival increased for patients diagnosed after 2008 for both STS (9.4%) and MFS (13.2%). There are differences between patient demographics and survival factors when comparing MFS to all STS. Monitoring changes in demographic and survival trends for rare STS subtypes like MFS is important to improve diagnostic algorithms and treatment options.

Fungating Soft Tissue Sarcoma: A Complex Treatment Dilemma.

Fungating soft tissue sarcoma (STS) occurs in up to 3.7% of STS cases, ulcerate or protrude directly from the skin. Several studies have examined past treatments and outcomes of patients with such tumors and suggest that management can be especially challenging. Considering this, it is plausible that fungating extremity tumors may warrant an individualized treatment approach that differs from standard treatment for non-fungating STS. We sought to examine treatment and outcome trends for fungating extremity STS to guide future treatment considerations. A comprehensive literature review of the PubMed database identified 1515 articles. Inclusion criteria included human subjects, adult population, extremity tumors and fungating tumors. Studies published prior to 1982 were excluded. 10 articles were relevant and met all criteria. Outcomes compare fungating STS with non-fungating STS. Patients with fungating STS are more likely to receive amputations as primary or secondary treatment (23-35 vs. 7.8-12%). Metastatic disease is more common among patients with fungating STS (20-33% vs. 9-15%). Patients with fungating STS have been found to have a higher likelihood of local recurrence (LR) (20.0% vs. 16.5%). 5-year overall survival (OS) is significantly decreased in patients with fungating STS (18.0-26.0% vs. 56.8-71.3%).Patients with fungating STS who receive limb sparing surgery (LSS) are more likely to require plastic surgical intervention (65% vs. 25%). Fungating STS is strongly associated with decreased mean time to death (13.8-16.2 months vs 29.0-30.4 months). Complication rates following surgical treatment of fungating STS are as high at 75% following amputation and 43% following LSS with up to 17% of those requiring reoperation. Infection and flap necrosis are the most common complications described. Though limited, current literature persistently reveals fungation as a poor prognostic factor for patients with soft tissue sarcoma. Expedient primarysurgical treatment may be appropriate given the higher metastatic potential and increased rate of complications associated with fungating STS. Limb salvage surgery is appropriate for primary, non-metastatic surgical treatment, though fungating tumors are treated with primary amputation more often than non-fungating STS, which may reduce postoperative complications in high-risk patients. Fungation is well established as an indication for palliative amputation. Increased rates of primary amputation in fungating STS may correspond to higher rates of metastatic disease at time of initial presentation for fungating STS. Timing of XRT should be carefully considered, as neoadjuvant XRTcoupled with a fungating tumor may result in a higher incidence of pre and postoperative complications and increased need for plastic surgical closure techniques. Adjuvant XRT is appropriate though used less often in patients with fungating STS.

Oncology

The October 2023 Oncology Roundup360 looks at: Are pathological fractures in patients with osteosarcoma associated with worse survival outcomes?; Spotting the difference: how secondary osteosarcoma manifests in retinoblastoma survivors versus conventional cases; Accuracy of MRI scans in predicting intra-articular joint involvement in high-grade sarcomas around the knee; Endoprosthetic reconstruction for lower extremity soft-tissue sarcomas with bone involvement; Local relapse of soft-tissue sarcoma of the extremities or trunk wall operated on with wide margins without radiation therapy; 3D-printed, custom-made prostheses in patients who had resection of tumours of the hand and foot; Long-term follow-up for low-grade chondrosarcoma; Evaluation of local recurrence and diagnostic discordance in chondrosarcoma patients undergoing preoperative biopsy; Radiological scoring and resection grade for intraosseous chondrosarcoma.

Hypofractionated Preoperative Radiotherapy 30Gy in Five Fractions for Soft Tissue Sarcoma of the Extremity

Hypofractionated preoperative radiotherapy (HypoRT) is being used with increasing frequency for soft tissue sarcomas (STS) of the extremities. Besides the social and economic advantages, HypoRT has a theoretical advantage in STS because of their low α/β ratio. The objective of this study is to review our experience using HypoRT to a dose of 30Gy in 5 fractions in STS of the extremities. This study is a retrospective review of patients with extremity STS treated at our center with preoperative HypoRT to a dose of 30Gy in 5 fractions given on alternate days over 2 weeks. Inclusion criteria were age ≥18 years, biopsy-proven primary STS in an extremity, and fitness for surgery. The primary endpoint was major wound complications (MWC) defined as the need for wound management or secondary operation under general or regional anesthesia within 120 days from surgery. Secondary objectives were: early toxicity grade ≥ 2 and clinical outcomes, including local control (LC), and metastasis-free survival (MFS). Descriptive statistics were used to evaluate patient and treatment characteristics. The Kaplan-Meier method was used to estimate survival. A total of 40 patients received preoperative HypoRT at our center between 2016 and 2022. The median age was 70 years (30 - 91). Males accounted for 57.5% of the patients. The most common primary site was the lower extremity (62.5%). The most prevalent histologic type was myxofibrosarcoma (27.5%), followed by pleomorphic spindle cell sarcoma (20%). All patients were treated with image-guided intensity modulated radiotherapy with margins for the CTV as tested in the RTOG 0630 study. Median follow-up was 14.8 months (5 - 86). Acute side effects were seen in 80% of the patients, all grade <3. The most common toxicity was dermatitis (37.5%), the second was fatigue (20%), and the third was pain (15%). Surgery was performed in all cases after a median interval from completion of HypoRT of 34 days (16-59). Amputation was performed in one patient with a fungating tumor, HypoRT having been aborted at only 24Gy because of worsening symptoms. On pathologic examination, positive margins were found in four cases (10%). The percentage of necrosis was ≥ 90% in 7 patients and 50%-90% in 10. MWC occurred in 13 patients (32.5%), including 10 who underwent a procedure with anesthesia. Sixteen patients were treated for a wound infection. Only one patient recurred locally. Two-year LC was 91.7%. MFS was 87.4% at 6 months and 60.8% at 2 years. DFS was 84.9% at 6 months and 64.8% at 2 years. The preoperative HypoRT regimen of 30Gy in 5 fractions given on alternate days for extremity STS is safe. Acute toxicity was not different from our previous experience using the conventional regimen of 50Gy in 25 fractions over 5 weeks and the MWC rate was comparable to that reported for the conventional regimen. Local control was excellent.

Surgical Outcomes in Patients Treated with 5-Day Preoperative Radiotherapy for Soft Tissue Sarcoma

Treatment for high-risk soft tissue sarcoma (STS) of the extremity/trunk includes radiation therapy (RT) and surgical resection. Initial results of a phase 2 single arm trial of 5-day preoperative RT demonstrated acceptable safety and local control. Here we report an update of detailed surgical outcomes among patients treated with 5-day preoperative RT alone on the original phase 2 study, as well as an ongoing expansion cohort. We conducted an updated analysis of surgical complications from a previously reported phase 2 trial of 50 patients with high-risk extremity/trunk STS treated with 5-day preoperative RT (30 Gy over 5 consecutive daily fractions) and surgery. The current analysis includes additional patients from an ongoing IRB-approved expansion cohort of the phase 2 study, which was designed to compare wound complication rates between patients receiving neoadjuvant chemotherapy and those receiving RT alone. However, given that the primary endpoint of this study has not matured, here we present only the data for patients treated with 5-day preoperative RT alone (n = 44; data cutoff date: February 17, 2022). We generated a secure prospective patient database and extracted data including demographic variables, cancer characteristics and surgical outcomes. Minimum post-operative follow-up was 90 days. Statistical analysis was performed using R (v4.2). From a total of 94 patients, mean age was 57 (17-90), 40 (42.5%) were female, 10 (10.6%) were diabetic and 8 patients (8.5%) were active smokers or had a >10 pack-year smoking history. Median follow up was 24 months (IQR 10.6-41.8). The most common histologic diagnosis was undifferentiated pleomorphic sarcoma (n = 38, 40.4%). The most common location was the lower extremity (n = 57, 60.6%). Overall, 26 (27.7%) patients experienced surgical wound complications. In the lower extremity, wound complications occurred in 18 patients (31.6%). In all other sites, wound complications occurred in 8 patients (21.6%) (p = 0.41). Twenty-seven (28.7%) cases required local tissue advancement for primary closure and 12 of these patients (44.4%) experienced a wound complication (p = 0.04). Wound dehiscence occurred in 18 patients at a median duration of 43.5 days (IQR 40.3-85.3) from surgery, comprising 69.2% of all wound complications. Secondary surgical intervention was required in 28 patients (29.8%), of which 7 were oncologic re-excisions and 15 were irrigation and debridement. On multivariate analysis, the use of advancement flaps (OR = 5.39; p = 0.004) and diabetes (OR = 4.08; p = 0.07) were associated with wound complications. Five-day preoperative RT for STS results in rates of wound complications comparable to standard fractionation. We identified local advancement flaps as the primary factor associated with wound complications. STS of the lower extremity that require complex closure warrant close attention for dehiscence.

Pre-Operative Radiotherapy in STS: Does Downsizing Matter?

Soft tissue sarcomas (STS) are a rare but insidious tumor that arises from mesenchymal tissue. Preoperative RT, followed by resection, is routinely used in extremity and truncal STS. The impact of RT on tumor volume and implications for prognosis is a great concern for patients, as changes in volume is often perceived as a reflection of treatment response. To date, data between tumor volume changes after RT and overall survival (OS) and distant metastasis-free survival (DMFS) in STS is sparse. In this study, we investigate changes in tumor volume after preoperative RT and its impact on OS and DMFS. Between 2000 and 2022, patients with stage I-III primary sarcoma of the extremity or trunk treated with pre-operative RT and wide resection were retrospectively reviewed from a prospective repository. Tumors were contoured using T2 sequences on MRIs within 2 weeks of initiation of RT and within 4 weeks post-RT. Tumor volume was determined using the medical image merge software. Univariate analysis (UVA) was performed using the log-rank test. Multivariate analysis (MVA) was performed using the Cox proportional hazards model. One hundred thirty-two patients had both pre- and post-RT MRIs available for contours. Median follow-up was 6 years. Median age at diagnosis was 56 years (range = 19-92). Most patients had stage III (73%) disease in the lower extremity (75%). The most common histology was undifferentiated sarcoma (30%). Median dose was 50 Gy in 25 fractions. Chemotherapy was administered in 44 (33%) patients. Median tumor volume prior to and after RT was 198 cc (range = 7.49 - 3899.87) and 225.21 cc (range = 0-9879.2), respectively. A decrease in tumor volume was seen in 90 patients (68%) from pre- to post-RT. In these patients, the mean percent change was -35%. Forty-two patients had an increase in tumor volume post-RT with a mean percent change of 56%. Overall local control was 98%. The 2- and 5-year OS were 89% and 76%, respectively. The 2- and 5-year DMFS was 76% and 70%, respectively. On UVA, increased age (p < 0.001), KPS ≤80 (p = 0.002), and smokers (p = 0.009) were associated with decreased OS. No variables were associated with DMFS. On MVA, age (p = 0.01) was associated with decreased OS and female gender (p = 0.03) and high-grade disease was associated with decreased DMFS (p = 0.04) Change in tumor volume did not impact OS (p = 0.15) or DMFS (p = 0.75). The 2- and 5-year DMFS for patients with a decrease in tumor volume was 79% and 71%, respectively. The 2 and 5-year DMFS for patients with an increase in tumor volume was 77% and 70%, respectively. The 2- and 5-year OS for patients with a decrease in tumor volume was 92% and 80%, respectively. The 2 and 5-year OS for patients with an increase in tumor volume was 83% and 69%, respectively. Change in tumor volume did not significantly impact OS and DMFS. Further studies with an increased sample size are warranted to corroborate these findings, however these results may assuage patient anxieties about the perceived tumor response to RT.

Radiomics Model for Predicting Pulmonary Metastasis in Sarcoma Patients

The lung is the most common site of metastasis in localized extremity soft tissue sarcomas (STS). Indeterminant lung nodules leads to challenges for both patients and providers. As such, accuracy in the diagnosis of pulmonary metastasis (PM) is important for clinical decision making. The purpose of this is study is to develop and evaluate a CT-based radiomic model to predict PM in sarcoma patients with indeterminate pulmonary nodules. Fifty-seven stage I-III sarcoma patients with indeterminate lung nodules on unenhanced CT that were approved for this study by our institution's internal review board (IRB). Twenty-two developed and categorized as PM and 35 without PM. A total number of 322 indeterminate nodules were investigated, where 165 & 157 nodules were from patients with and without PM, respectively. A total of 96 radiomic features (RF) (including first order statistics, 2d shape features, gray level co-occurrence, gray level size zone, gray level run length, neighboring gray tone difference & gray level dependence matrices) were taken from unenhanced CT images of each patient. We included 2D shape features since the size and shape of indeterminate lung nodules may have some correlation with PM. Spearman correlation were used to rule out redundant features (r2>0.9). T-test statistics was used to determine feature with significant differences that can differentiate responders with and without PM. Support Vector Machine (SVM) model was fitted to combinations of groups of 2-3 radiomic features. The AUC of the ROC curve was used to evaluate the model performance. Pointwise confidence intervals (CI) for AUC were calculated using 100 bootstrap replicates. Four features were found significant after Spearman correlation and T-test statistical testing: 1. Maximum (MAX); 2. Minor Axis Length (MAL); 3. Gray Level Non-uniformity (GLNU); and 4. Interquartile Range (IR). The best performing 2-feature radiomic SVM model had an AUC of 0.69 (95% CI 0.61,0.74) for the MAX and GLNU features. The best performing 3-feature radiomic SVM model had an AUC of 0.74 (95% CI 0.70,0.80) for the MAX, MAL and IR features. CT-based radiomics model has the potential to be used to predict PM in sarcoma patients presenting with indeterminate lung nodules. Additional research will focus on investigating derived parameters for existing RF, such as the ratio of the max RF to mean RF, to see if they improve the predictive performance of the model, as well as testing the models on external patient cohort. These radiomic models could be useful tools in guiding PM screening and providing a patient specific monitoring of sarcoma patients.

The incidence, risk factors and outcomes of wound complications after preoperative radiotherapy and surgery for high grade extremity soft tissue sarcomas: A 14-year retrospective study

ObjectiveThe aim of this study was to analyze the wound complication (WC) rate and to determine the risk factors for WC in patients with soft tissue sarcoma treated with preoperative radiotherapy followed by surgical resection. MethodsUsing the database of Oxford University Hospital (OUH) we retrospectively studied 126 cases of soft tissue sarcomas treated with preoperative radiotherapy and surgery between 2007 and 2021. WC were defined as minor wound complication (MiWC) not requiring surgical intervention or major wound complication (MaWC) if they received a secondary surgical intervention. Univariate and multiple regression analyses were performed using frequency of WC and MaWC as a dependent variable. ResultsThe incidence of WC and MaWC was 43.7% (55/126) and 19% (24/126). Age (OR:1.03, 95%CI: 1.00–1.06, p = 0.016), tumor size (OR:1.11, 95%CI:1.01–1.21, p = 0.027) and tumor site namely proximal lower limb vs upper limb (OR:10.87, 95%CI 1.15–103.03, p = 0.038) were risk factors on multivariate analysis. In nested case control analysis, the incidence of MaWC was 43.6% (24/55), the mean recovery time is 143 days in patients with MaWC. Smoking increases the risk for MaWC (OR:8.32, 95%CI:1.36–49.99, p = 0.022). The time interval between surgery and wound complication reduces the risk for MaWC (OR:0.91, 95%CI:0.84–0.99, p = 0.028) in multivariate analysis. ConclusionsAge, tumor site and size are risk factors for WC requiring preoperative radiotherapy. Smoking and the time interval between surgery and wound complication are risk factors for MaWC as compared with MiWC. MaWC rate (19%) are comparable to those in postoperative radiotherapy and surgery alone.