Trunk Wall Research Articles

Evaluation of Two Different Approaches for Selecting Patients for Postoperative Radiotherapy in Deep-Seated High-Grade Soft Tissue Sarcomas in the Extremities and Trunk Wall.

Two national sarcoma centers have had different approaches for selecting patients with grade 2-3 deep-seated soft tissue sarcomas (STS) for postoperative radiotherapy (RT). We evaluated potential differences in local recurrence in patients treated at the two centers. At Sarcoma Center 1 (SC1), RT was the standard treatment for all tumors except certain small tumors excised with a margin wider than 1 cm. Sarcoma Center 2 (SC2) avoided RT for tumors regardless of tumor size if removed with a margin wider than 1 cm and/or a solid barrier. We included 386 patients (SC1/SC2 = 196/190) over 18 years of age diagnosed with a non-metastatic grade 2-3, deep-seated STS of the extremities or trunk wall, who underwent primary surgical treatment (only tumors excised with a negative margin) from 1 January 2000, to 31 December 2016. Kaplan-Meier survival analysis, competing risk analysis, and cause-specific Cox regression were applied. A total of 284 patients received primary RT, 163 (83%) at SC1 and 121 (64%) at SC2 (p < 0.001). The cumulative incidence of local recurrence at five years was 15% (95% CI: 10-19%) at SC1 and 14% (95% CI: 9-19%) at SC2. Multivariate analysis showed no significant differences in local recurrence between the centers. We concluded that when entering all available patients into the analysis using an intention-to-treat principle, a more selective approach to postoperative RT in patients with grade 2-3 deep-seated STS did not lead to a higher local recurrence rate. However, with this study design, we cannot rule out if the local recurrence rate could have been lower if RT was administered to all tumors removed with a margin wider than 1 cm and/or a solid barrier.

1737P A comparison of the risk prediction models sarculator and PERSARC in patients with localized soft tissue sarcoma of the extremities and trunk wall

1737P A comparison of the risk prediction models sarculator and PERSARC in patients with localized soft tissue sarcoma of the extremities and trunk wall

Proteomic profiling improves prognostic risk stratification of the Sarculator nomogram in soft tissue sarcomas of the extremities and trunk wall.

High-risk soft tissue sarcomas of the extremities and trunk wall (eSTS), as defined by the Sarculator nomogram, are more likely to benefit from (neo)adjuvant anthracycline-based therapy compared to low/intermediate-risk patients. The biology underpinning these differential treatment outcomes remain unknown. We analysed proteomic profiles and clinical outcomes of 123 eSTS patients. A Cox model for overall survival including the Sarculator was fitted to individual data to define four risk groups. A DNA replication protein signature-Sarcoma Proteomic Module 6 (SPM6) was evaluated for association with clinicopathological factors and risk groups. SPM6 was added as a covariate together with Sarculator in a multivariable Cox model to assess improvement in prognostic risk stratification. DNA replication and cell cycle proteins were upregulated in high-risk versus very low-risk patients. Evaluation of the functional effects of CRISPR-Cas9 gene knockdown of proteins enriched in high-risk patients using the cancer cell line encyclopaedia database identified candidate drug targets. SPM6 was significantly associated with tumour malignancy grade (p = 1.6e-06), histology (p = 1.4e-05) and risk groups (p = 2.6e-06). Cox model analysis showed that SPM6 substantially contributed to a better calibration of the Sarculator nomogram (Index of Prediction Accuracy = 0.109 for Sarculator alone versus 0.165 for Sarculator + SPM6). Risk stratification of patient with STS is defined by distinct biological pathways across a range of cancer hallmarks. Incorporation of SPM6 protein signature improves prognostic risk stratification of the Sarculator nomogram. This study highlights the utility of integrating protein signatures for the development of next-generation nomograms.

Treatment of giant neurofibromas in extremities and trunk wall of neurofibromatosis type 1 patients: a Chinese 12-year single-institution experience.

Giant neurofibromas occurring in individuals diagnosed with neurofibromatosis type 1 (NF1) often result in considerable disfigurement, functional impairment, and diminished quality of life. Although debulking surgery poses inherent risks of complications, it remains the most efficacious approach to address these issues. The primary objective of this study was to share our surgical experience with giant neurofibromas in the extremities and trunk wall of NF1 patients which may help surgeons to minimize intraoperative bleeding and facilitate tumor excision. A retrospective review was conducted at a single center, encompassing 36 NF1 patients with giant neurofibromas in the extremities and trunk wall who underwent debulking surgery from July 2010 to July 2022. Twenty-one male and fifteen female NF1 patients who received one to four surgical interventions were evaluated. The average age at the time of surgery was 17.8 years. The median follow-up time was 52 months. Our findings revealed relatively low rates of complications and recurrence. Notably, patients expressed satisfaction with both the aesthetic and functional results. Debulking surgery of giant neurofibromas in the extremities and trunk wall of NF1 patients can effectively reduce the tumor burden, leading to improvements in both the appearance and function.

Pulmonary artery sarcoma affecting the pulmonary valve mistaken as pulmonary vasculitis: a case report and comparative literature review

Pulmonary arterial sarcomas (PAS) are rare aggressive tumours occurring mainly in the pulmonary trunk. We report a case of PAS involving the pulmonary trunk wall and valve, with uniform wall thickening which represents an atypical imaging manifestation of this tumour. A 63-year-old male presented with vague respiratory symptoms with rapid progression. CTPA showed low density filling defects in both pulmonary arteries and PET scan showed increased uptake in the pulmonary trunk, which along with raised ESR suggested Pulmonary Vasculitis. Echo imaging showed Right ventricular hypertrophy and pulmonary stenosis. Response to steroid therapy was minimal and his symptoms worsened. A referral for second opinion was made and he was diagnosed with PAS. He underwent Pulmonary thromboendarterectomy with Pulmonary valve replacement. Post-operative histopathology confirmed the diagnosis. PAS is rare and frequently misdiagnosed. Surgical resection is not curative, but together with chemotherapy can prolong survival.

Unplanned Resections of Soft Tissue Sarcomas-Necessity of Re-Resection?

In soft tissue sarcomas, unplanned resections, or so-called Whoops procedures, do occur quite frequently, thus primarily owing to the abundant presence of benign lesions. Whether re-resection reduces local recurrence or improves overall survival remains a topic of ongoing debate. The principle objective of this study was to analyze the outcomes of patients with soft tissue sarcomas of the extremities or trunk wall after an incidental marginal resection by comparing re-resections to individuals who declined the procedure. A total of 185 patients who underwent unplanned resection were included. These patients were stratified into two groups: Group A (n = 156) underwent re-excision, while Group B (n = 29) was treated conservatively. Depending on the clinical scenario, radio- or chemotherapy was either administered in a neoadjuvant or an adjuvant setting. The presence of residual tumor and metastatic disease was documented. Clinical outcomes, specifically local recurrence (LR), local recurrence-free survival (LRFS) and overall survival (OS), were utilized for evaluation. Group B exhibited significantly larger tumors (p < 0.0001) and a higher mean age than Group A. Among the patients in Group A, 11 (5.9%) had contaminated resection margins (R1), and residual disease (RD) was observed in 93 (59.6%) of the resected specimens. In group B, 10 patients received adjuvant radiotherapy alone, 5 received chemotherapy alone, and 13 underwent a combined approach consisting of both radio- and chemotherapy. In Group A, 8% (n = 12) of the patients developed local recurrence (LR) during the observation period. Conversely, in Group B, this amount was 14% (n = 4) (n.s.). Of the 12 LR in Group A, 10 were found in the subgroup with residual disease. Overall survival and local recurrence-free survival were not significantly different between the groups. A total of 15% (n = 24) of the patients in Group A developed metastatic disease, while 10% (n = 3) in Group B developed metastatic disease (n.s.). Following the reresection of unplanned resected STS, there was no statistically significant difference observed in overall survival or LR compared to patients who did not undergo re-resection. However, within the subgroup of patients with residual disease in the re-resected specimen, the OS was compromised, and the LR rate was higher. Particularly for low-grade lesions, adopting a more conservative approach seems to be justified.

Regional hyperthermia for soft tissue sarcoma – a survey on current practice, controversies and consensus among 12 European centers

Purpose To analyze the current practice of regional hyperthermia (RHT) for soft tissue sarcoma (STS) at 12 European centers to provide an overview, find consensuses and identify controversies necessary for future guidelines and clinical trials. Methods In this cross-sectional survey study, a 27-item questionnaire assessing clinical subjects and procedural details on RHT for STS was distributed to 12 European cancer centers for RHT. Results We have identified seven controversies and five consensus points. Of 12 centers, 6 offer both, RHT with chemotherapy (CTX) or with radiotherapy (RT). Two centers only offer RHT with CTX and four centers only offer RHT with RT. All 12 centers apply RHT for localized, high-risk STS of the extremities, trunk wall and retroperitoneum. However, eight centers also use RHT in metastatic STS, five in palliative STS, eight for superficial STS and six for low-grade STS. Pretherapeutic imaging for RHT treatment planning is used by 10 centers, 9 centers set 40–43 °C as the intratumoral target temperature, and all centers use skin detectors or probes in body orifices for thermometry. Discussion There is disagreement regarding the integration of RHT in contemporary interdisciplinary care of STS patients. Many clinical controversies exist that require a standardized consensus guideline and innovative study ideas. At the same time, our data has shown that existing guidelines and decades of experience with the technique of RHT have mostly standardized procedural aspects. Conclusions The provided results may serve as a basis for future guidelines and inform future clinical trials for RHT in STS patients.

Favorable clinical efficacy of cytotoxic chemotherapy in patients with progressive desmoid tumors: a retrospective real-world study.

The real-world evidence about the efficacy of cytotoxic chemotherapy in desmoid tumors is still limited. We investigated the efficacy of chemotherapy in the treatment of recurrent or progressive desmoid tumors. The patients with desmoid tumors who had received cytotoxic chemotherapy between November 2007 and June 2020 in two tertiary hospitals in Korea were reviewed. A total of 25 patients were included in the analysis. The most common primary tumor site was the intra-abdominal or pelvic cavity (56%), followed by the trunk and abdominal wall (24%), extremities (16%), and head and neck (4%). Sixty percent of the patients had familial adenomatous polyposis and 76% received doxorubicin plus dacarbazine. The objective response rate and disease control rate was 64% (95% confidence interval [CI]: 40.7-82.8) and 96% (95% CI: 77.2-99.9), respectively. With the median follow-up time of 55months (95% CI: 41.0-68.2), the 3-year PFS rate was 65% (95% CI: 41.1-80.5), and the 3-year OS rate was 89% (95% CI: 63.8-97.3). Grade 3 or 4 hematologic adverse events were reported in 14 patients, all of which were manageable. Our real-world evidence suggests that doxorubicin-based cytotoxic chemotherapy can be an effective treatment option for recurrent and progressive desmoid tumors with respect to favorable clinical outcomes.

Radiotherapy versus limb-sparing surgery alone in low-grade soft-tissue sarcoma of the extremity and trunk wall: a systematic review and meta-analysis.

Current guidelines recommend the use of radiotherapy in the management of intermediate and high-grade soft-tissue sarcoma of the extremity and trunk wall. Its use in low-grade sarcoma is less clear. To date there have been no pooled data analyses regarding its role in this context. Its use is not without complications and therefore must be justified. We aim to assess the oncological impact of radiotherapy versus limb-sparing surgery alone in this subset of sarcoma. Medline, EMBASE and Cochrane's databases were searched from 1982 to present. Studies on or having a subgroup analysis of low-grade soft tissue sarcoma, with a radiotherapy and a surgery only arm were included. Outcomes included local recurrence and overall survival. Patients were at least 16 years of age with primary de-novo sarcoma who had not undergone prior resection or treatment. Those undergoing concomitant therapy were excluded. Data extraction was performed independently by two reviewers. Results were pooled using a random-effects model and presented as a forest plot. Primary outcome measures included local recurrence and overall survival. Eleven unique studies were included, consisting of two RCTs and nine non-randomized studies. Overall, there were 12 799 patients. Four studies were included in meta-analysis and the overall pooled effect showed a limited role of radiotherapy in overall survival outcomes when compared to limb-sparing surgery alone HR 1.00 [0.83-1.20] P = 0.41. Descriptive analysis suggests there is limited role of radiotherapy in improving local recurrence outcomes. This study suggests there is limited role for radiotherapy versus limb-sparing surgery alone in low-grade soft-tissue sarcoma. These findings strongly suggest there is lack of high-quality data and that further research must be undertaken prior to forming any strong conclusions regarding the management of low-grade soft-tissue sarcoma. Demonstrating a role for radiotherapy may help improve the quality of excisional margins and thus potentiate limb-sparing surgery.

Inflammatory Rhabdomyoblastic Tumor: Clinicopathologic and Molecular Analysis of 13 Cases

Inflammatory rhabdomyoblastic tumors (IRMTs) are newly recognized skeletal muscle tumors with uncertain malignant potential. We investigated 13 IRMTs using clinicopathologic, genetic, and epigenetic methods. The cohort included 7 men and 6 women, aged 23 to 80 years (median, 50 years), of whom 2 had neurofibromatosis type 1. Most tumors occurred in the deep soft tissues of the lower limbs, head/neck, trunk wall, and retroperitoneum/pelvis. Two tumors involved the hypopharyngeal submucosa as polypoid masses. Eight tumors showed conventional histology of predominantly spindled cells with nuclear atypia, low mitotic activity, and massive inflammatory infiltrates. Three tumors showed atypical histology, including uniform epithelioid or plump cells and mitotically active histiocytes. The remaining 2 tumors demonstrated malignant progression to rhabdomyosarcoma; one had additional IRMT histology and the other was a pure sarcoma. All 11 IRMTs without malignant progression exhibited indolent behavior at a median follow-up of 43 months. One of the 2 patients with IRMTs with malignant progression died of lung metastases. All IRMTs were positive for desmin and PAX7, whereas myogenin and MyoD1 were expressed in a subset of cases. Targeted next-generation sequencing identified pathogenic mutations in NF1 (5/8) and TP53 (4/8). All TP53 mutations co-occurred with NF1 mutations. TP53 variant allele frequency was much lower than that of NF1 in 2 cases. These tumors showed geographic (subclonal) strong p53 immunoreactivity, suggesting the secondary emergence of a TP53-mutant clone. DNA methylation–based copy number analysis conducted in 11 tumors revealed characteristic flat patterns with relative gains, including chromosomes 5, 18, 20, 21, and/or 22 in most cases. Widespread loss of heterozygosity with retained biparental copies of these chromosomes was confirmed in 4 tumors analyzed via allele-specific profiling. Based on unsupervised DNA methylation analysis, none of the 11 tumors tested clustered with existing reference entities but formed a coherent group, although its specificity warrants further study.

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.

Pathological and radiological response following neoadjuvant treatments in primary localized resectable myxofibrosarcoma and undifferentiated pleomorphic sarcoma of the extremities and trunk wall.

To explore the correlation between pathological and radiological response to preoperative treatments and outcome in surgically treated patients with myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS). All consecutive patients with primary localized MFS and UPS of the extremities and trunk wall surgically treated with curative intent at our center (2005-2021) were included. Clinical data including residual visible tumor (VT%) on surgical specimen and Response Evaluation Criteria in Solid Tumor (RECIST) were retrieved. Kaplan-Meier curves for overall survival and disease-free survival, and cumulative incidence of local relapse and distant metastasis were estimated in a competing risk framework according to RECIST and VT%, overall and by treatment group. Cox and Fine and Gray multivariable models were performed. Of 693 patients affected by primary MFS and UPS, 233 (66 MFS and 167 UPS) were treated by neoadjuvant chemotherapy (naChT), radiotherapy (naRT), or both (naChT-RT). VT% was ≤5% in 13/46 (28.2%), 24/99 (24.2%), and 40/88 (45.4%) patients, respectively. There were 11/46 (29.7%), 22/99 (22.7%), and 23/88 (26.1%) RECIST partial responses and 18/46 (48.6%), 59/99 (60.8%), and 60/88 (68.2%) RECIST stable disease, respectively. In naChT, a trend for a better survival was observed when VT% ≤5% (p=.09), whereas RECIST partial responses and stable disease had the same outcome. VT% was not associated with outcome in naRT or naChT-RT, whereas RECIST response was. In primary localized MFS and UPS treated with neoadjuvant therapies, VT% seems more relevant than size reduction after naChT, whereas the opposite is true when naRT is administered alone or concurrent to ChT.

Deep learning with whole slides images to predict histological response to neoadjuvant chemotherapy in patients with resectable high grade soft-tissue sarcomas: A multicenter study.

11512 Background: Two recent randomized trials have confirmed the potential benefit of neoadjuvant anthracycline-based chemotherapy in patients with high-grade soft-tissue sarcomas (STS) (Issels et al 2018, Gronchi et al 2017). However, as for adjuvant chemotherapy, the main issue with neoadjuvant treatment of STS patients is the identification of predictive factors of response to chemotherapy that could avoid for a majority of patients ineffective and potentially toxic treatment with impaired quality of life. Histological response, defined as the percentage of stainable tumor cells on the surgical specimen, has been shown to be a reliable surrogate for metastasis-free survival and overall survival in bone but also in soft-tissue sarcomas (Crombe et al JCO Clin Inf 2021). Developing a tool to help medical oncologists predict the potential benefit of neoadjuvant chemotherapy prior to starting the treatment would be of great value for precision medicine in sarcomas. To address this need, we propose a deep learning-based approach to predict histological response to neoadjuvant chemotherapy patients from routine histological whole slide images sampled at diagnosis. Methods: A cohort of 220 patients with high grade limb and trunk wall STS enrolled in the NEOSARCOMICS study (NCT02789384, sponsor: Institut Bergonié, Bordeaux, France) was used to train a model to predict the binarized histological response from diagnostic biopsies. Responders are defined by a histological response inferior or equal to 10%. Digitized hematoxylin/eosin slides were preprocessed to segment the tissue and decompose the image into patches of smaller resolution. Features were extracted from each patch using a Vision Transformer pretrained in a self-supervised fashion on histology slides. A Multiple Instance Learning model was trained on the resulting features to compute a prediction at the patient level. The algorithm was trained and validated through a 5-fold, 5-repeat cross-validation scheme. Finally, external validation is performed on an unseen cohort from Centre Léon Bérard to assess the robustness of the model. Results: To predict histological response to neoadjuvant chemotherapy, a model using only diagnostic biopsies achieved an AUC of 0.69 (95% confidence interval, 0.60-0.76). External validation is ongoing and shows promising preliminary results with an AUC of 0.67 (95% confidence interval with bootstrapping, 0.45-0.89). Conclusions: This multi-center study demonstrates that deep-learning models can accurately predict the histological response to neoadjuvant chemotherapy from routine histological whole slide images sampled at diagnosis. This model could be used as a pre-screening tool to improve patient selection for neoadjuvant chemotherapy in STS.

Comparison of In-service Reduced vs. Full Torso Coverage Armor for Females.

Body armor and torso-borne equipment are critical to the survivability and operational effectiveness of a soldier. Historically, in-service designs have been predominantly designed for males or unisex, which may be disadvantageous for females who are shaped differently and, on average, smaller in stature and mass than their male counterparts. This study assesses the biomechanical and performance impact of two Canadian in-service armors and fighting load conditions on females. Four tasks (i.e., range of motion, treadmill march [×2], and a wall obstacle) were performed in a Baseline condition and two in-service torso-borne equipment conditions; the full torso coverage (FTC) condition has full upper torso soft armor with the fighting load carried in a separate vest, while the reduced coverage (RC) has a plate carrier with fighting load integrated into the armor carrier, bulk positioned higher, and less torso coverage. Both used identical combat loads and front and back armor plates. Trunk range of motion, march lower limb kinematics, march shoulder and hip skin pressures, perceived discomfort after the march, and time to traverse a wall obstacle were captured. Data were collected to assess the biomechanics and usability of the systems for eight females, representative of military recruits. Linear mixed-effects models were created, and analysis of variances (ANOVAs) were then performed on all the outcome measures (P < .05). Tukey's post-hoc procedures were performed when appropriate (P < .05). There were significant differences between the RC and FTC for the sit and reach test (P < .001), lateral bend test (P < .001), and wall traverse time (P < .01). In all cases, the RC outperformed FTC. There were no differences between the two in-service conditions with respect to hip, knee, and ankle flexion/extension. The RC average skin pressure was higher than the FTC at the left and right shoulders by 103% and 79%, respectively, and peak skin pressure at the left shoulder by 75%. Both in-service conditions showed decrements in performance from Baseline for sit and reach (P < .001), lateral bend (P < .001), and peak hip and knee flexion (P < .01) with the FTC showing decreases in trunk rotation (P < .001) and wall traverse time (P < .01). Improved outcomes for the RC can be attributed to design differences. The lower placement of bulk in FTC may act as a physical barrier during range of motion tasks and the wall obstacle. The presence of shoulder caps on FTC provides another physical barrier that likely impedes full movement through the arms and shoulders. While the narrower shoulder straps of the RC remove the barrier, it causes more concentrated skin pressures on the shoulder that can lead to injury. The results suggest that the RC offers a potential for increased operational effectiveness in females (and potentially for males) compared to the FTC system. Shoulder pressure, an important predictor of discomfort and injury, is the only measure for which FTC outperformed the RC. Future torso-borne equipment designs targeting this outcome measure could help increase the effectiveness of the RC and other similar systems that reduce torso coverage, though survivability implications must also be considered.

Patterns of Failure in High-Grade Soft Tissue Sarcomas of the Extremities and Trunk Wall After Pre- or Postoperative Radiation Therapy

Radiotherapy (RT) is a mainstay of treatment for high-grade soft tissue sarcomas (STS). We sought to examine the pattern of local recurrence (LR) with regard to target volume, clinical course, and tumor characteristics in extremity and trunk wall STS patients receiving pre- or postoperative RT. In this retrospective study, LR rates and patterns in 91 adult patients with a primary diagnosis of localized high-grade STS of the extremities and trunk wall treated with pre- or postoperative RT at our institution between 2004 and 2021 were analyzed. Radiation treatment plans and imaging data sets at diagnosis and LR were compared. Seventeen out of 91 (18.7 %) patients developed a LR after a median time of 12.7 months. In 10 out of 13 LRs (76.9%) with available treatment plans and radiographic imaging data at the time of recurrence, the LR occurred within the planned target volume (PTV), 2 LRs were marginal (15.4%, at the edge of the PTV volume), and one relapsed out-of-field (7.7%, outside the PTV volume). Positive surgical margins (microscopic or macroscopic) were found in 5 out of 91 patients (5.5%), 1 of which was found in the 17 patients with LRs (5.9%). Eleven of 13 LR patients (84.6%) with available treatment plans and radiographic imaging data received postoperative RT; the median total RT dose was 60 Gy. Volumetric-modulated arc therapy was used in 10 (76.9%), intensity-modulated RT in 2 (15.4%), and 3-dimensional conformal radiation therapy in 1 (7.7%) of 13 LRs. The majority of LRs occurred within the PTV suggesting that LR is most likely not a consequence of inadequate target volume definition, but rather of radioresistant tumor biology. To further improve local tumor control, future research on the potential of dose escalation with normal tissue sparing, STS subtype-specific tumor biology, radiosensitivity, and surgical technique is indicated.

Local relapse of soft tissue sarcoma of the extremities or trunk wall operated on with wide margins without radiation therapy.

The quality of surgical margins is the most important factor affecting local control in soft tissue sarcoma (STS). Despite this, there is no universally accepted consensus on the definition of an adequate surgical margin or on which patients should be offered radiation therapy. This study focuses on local control and its prognostic factors in patients with trunk wall and extremity STS. Adult patients with a final diagnosis of trunk wall or extremity STS referred to a single tertiary referral centre between August 1987 and December 2016 were identified from a prospective institutional database. Patients were treated according to a protocol instituted in 1987. The classification of surgical margins and indications for radiation therapy were based on anatomy and strict definition of surgical margins as metric distance to the resection border. Local treatment was defined as adequate if patients received either surgery with wide margins alone or marginal surgery combined with radiation therapy. Margins were considered wide if the tumour was excised with pathological margins greater than 2.5 cm or with an uninvolved natural anatomical barrier. After treatment, patients were followed up with local imaging and chest X-ray: 5 years for high-grade STS, 10 years for low-grade STS. A total of 812 patients were included with a median follow-up of 5.8 (range 0.5-19.5) years. Forty-four patients had a grade 1 tumour: there were no instances of recurrence in this group thus they were excluded from further analysis. Five-year local control in the 768 patients with grade 2-3 STS was 90.1 per cent in patients receiving adequate local treatment according to the protocol. Altogether, 333 patients (43.4 per cent) were treated with wide surgery alone and their 5-year local control rate was 91.1 per cent. Among patients treated with wide surgery alone, deep location was the only factor adversely associated with local relapse risk in multivariable analysis; 5-year local control was 95.3 per cent in superficial and 88.3 per cent in deep-sited sarcomas (hazards ratio 3.154 (95% c.i. 1.265 to 7.860), P = 0.014). A high local control rate is achievable with surgery alone for a substantial proportion of patients with STS of the extremities or superficial trunk wall.

Correlation of radiological and histopathological response after neoadjuvant radiotherapy in soft tissue sarcoma

Background The aim of this study was to assess the association between radiological and histopathological response after neoadjuvant radiotherapy (nRT) in soft tissue sarcoma (STS), as well as the prognostic value of the different response evaluation methods on the oncological outcome. Methods A retrospective cohort of patients with localized STS of the extremity and trunk wall, treated with nRT followed by resection were included. The radiological response was assessed by RECIST 1.1 (RECIST) and MR-adapted Choi (Choi), histopathologic response was evaluated according to the EORTC-STBSG recommendations. Oncological outcome parameters of interest were local recurrence-free survival (LRFS), disease metastases-free survival (DMFS), and overall survival (OS). Results For 107 patients, complete pre- and postoperative pathology and imaging datasets were available. Most tumors were high-grade (77%) and the most common histological subtypes were undifferentiated pleomorphic sarcoma/not otherwise specified (UPS/NOS, 40%), myxoid liposarcoma (MLS, 21%) and myxofibrosarcoma (MFS, 16%). When comparing RECIST to Choi, the response was differently categorized in 58%, with a higher response rate (CR + PR) with Choi. Radiological responders showed a significant lower median percentage of viable cells (RECIST p = .050, Choi p = .015) and necrosis (RECIST p < .001), and a higher median percentage of fibrosis (RECIST p = .005, Choi p = .008), compared to radiological non-responders (SD + PD). RECIST, Choi, fibrosis, and viable cells were not significantly associated with altered oncological outcome, more necrosis was associated with poorer OS (p = .038). Conclusion RECIST, Choi and the EORTC-STBSG response score show incongruent results in response evaluation. The radiological response was significantly correlated with a lower percentage of viable cells and necrosis, but a higher percentage of fibrosis. Apart from necrosis, radiological nor other histopathological parameters were associated with oncologic outcomes.

Immune-cell infiltration in high-grade soft tissue sarcomas; prognostic implications of tumor-associated macrophages and B-cells

Background Soft tissue sarcomas are rare, morphologically, and genetically heterogenous. Though the tumors display abundant tumor stroma with infiltrating immune cells, the prognostic impact of various immunologic markers in sarcoma remains poorly defined. We aimed to characterize the immune landscape of a treatment-naïve cohort of soft tissue sarcoma of the extremities and the trunk wall with correlations to metastasis-free survival. Materials and Methods We surveyed immunohistochemical expression patterns for CD163, CD20, CD3, CD8, and FOXP3 in 134 adult high-grade leiomyosarcomas, liposarcomas, and synovial sarcomas. Results Macrophages outnumbered tumor-infiltrating lymphocytes. High CD163 infiltration was identified in 49% of the tumors and was overrepresented (66%) in leiomyosarcoma compared to liposarcoma (46%) and synovial sarcoma (9%). Tumor-grade also correlated with CD163 positivity with high expression in 53% of the high-grade lesions and 28% in low-grade tumors. Infiltrating CD3, CD8 and FOXP3-positive T-cells were significantly more prevalent in leiomyosarcomas than in liposarcomas/synovial sarcomas. CD20+ B-cells were identified only in 14% of the STS. Correlation to established prognostic factors revealed a correlation between CD163+ macrophages and necrosis and predicted an increased risk of metastases. No correlation between CD20+ B-cells and known prognostic factors could be established, though CD20+ B-cells infiltration predicted improved overall survival. Conclusion We confirm that tumor-infiltrating macrophages outnumber tumor-infiltrating lymphocytes in soft tissue sarcoma and signify an increased risk of metastasis. CD20+ B-cells are scarce in STS and correlate to improved survival. To date, immunotherapeutic strategies directed against T-cells have shown limited effect in soft tissue sarcoma. Our observations suggest that immunomodulatory agents focusing on macrophages may be worthwhile for further investigations in this tumor type. Further studies exploring the prognostic and predictive significance of CD20+ B cells are warranted.

Role of perioperative chemotherapy and radiotherapy for localized high-grade malignant peripheral nerve sheath tumor at the extremities and trunk wall: a population-based cohort study.

Primary tumor resection is the mainstay of treatment for malignant peripheral nerve sheath tumors. However, the efficacy of perioperative chemotherapy and radiotherapy for malignant peripheral nerve sheath tumors has not been elucidated. This retrospective analysis based on a Japanese registry included patients with localized malignant peripheral nerve sheath tumors arising at the extremities and trunk wall. Disease-specific overall survival and local recurrence-free survival were estimated using the Kaplan-Meier method. A Cox regression model was used to identify prognostic factors. Characteristics of groups with or without chemotherapy were adjusted using propensity score matching. In total, 291 patients were included. The 5-year disease-specific overall survival rate was 70.6%. Multivariate analysis of disease-specific overall survival revealed that deep-seated tumors were a poor prognostic factor, but perioperative chemotherapy was not associated with disease-specific overall survival (hazard ratio, 0.81; 95% confidence interval, 0.45-1.43, P=0.46). Local recurrence was observed in 55 patients (19.0%), and surgical margins (R1 and R2) were significant risk factors. Overall, perioperative chemotherapy did not prolong disease-specific overall survival (5-year disease-specific overall survival: 74.1% vs. 69.3%, P=0.75) and had limited efficacy in the group with tumor size≥5cm, although the difference was not statistically significant (5-year disease-specific overall survival: 77.2% vs. 68.6%, respectively, P=0.13). After adjustment by propensity score matching, perioperative chemotherapy significantly prolonged disease-specific overall survival (5-year disease-specific overall survival: 74.9% vs. 57.1%, P=0.03), but this effect was not observed in local recurrence-free survival. In all patients, perioperative radiotherapy did not correlate with local recurrence-free survival (hazard ratio, 1.43; 95% confidence interval 0.78-2.62, P=0.25). Perioperative chemotherapy had limited efficacy for disease-specific overall survival in patients with localized malignant peripheral nerve sheath tumors.

Overall survival in patients with re-excision of positive microscopic margins of limb and trunk wall soft tissue sarcoma operated outside of a reference center: a nationwide cohort analysis

BackgroundThis French nationwide NETSARC exhaustive prospective cohort aims to explore the impact of systematic re-excision (RE) as adjuvant care on overall survival (OS), local recurrence free survival (LRFS), and local and distant control (RFS) in patients with soft tissue sarcoma (STS) with positive microscopic margins (R1) after initial resection performed outside of a reference center.MethodsEligible patients had experienced STS surgery outside a reference center from 2010 to 2017, and had R1 margins after initial surgery. Characteristics and treatment comparisons used chi-square for categorical variables and Kruskall-Wallis test for continuous data. Survival distributions were compared in patients reexcised (RE) or not (No-RE) using a log-rank test. A Cox proportional hazard model was used for subgroup analysis.ResultsA total of 1,284 patients had experienced initial STS surgery outside NETSARC with R1 margins, including 1,029 patients with second operation documented. Among the latter, 698 patients experienced re-excision, and 331 were not re-excised. Characteristics were significantly different regarding patient age, tumor site, tumor size, tumor depth, and histotype in the population of patients re-excised (RE) or not (No-RE). The study identified RE as an independent favorable factor for OS (HR 0.36, 95%CI 0.23–0.56, p<0.0001), for LRFS (HR 0.45, 95%CI 0.36–0.56, p<0.0001), and for RFS (HR 0.35, 95%CI 0.26–0.46, p<0.0001).ConclusionThis large nationwide series shows that RE improved overall survival in patients with STS of extremities and trunk wall, with prior R1 resection performed outside of a reference center. RE as part of adjuvant care should be systematically considered.Level of evidence II