Trunk Wall Soft Tissue Sarcoma Research Articles

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.

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.

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

ASO Author Reflections: Outcome Improvement Over Time in Extremity and Trunk Wall Soft Tissue Sarcomas: To Whom the Merit?

ASO Author Reflections: Outcome Improvement Over Time in Extremity and Trunk Wall Soft Tissue Sarcomas: To Whom the Merit?

Prognosis prediction of extremity and trunk wall soft-tissue sarcomas treated with surgical resection with radiomic analysis based on random survival forest.

Many researches have applied machine learning methods to find associations between radiomic features and clinical outcomes. Random survival forests (RSF), as an accurate classifier, sort all candidate variables as the rank of importance values. There was no study concerning on finding radiomic predictors in patients with extremity and trunk wall soft-tissue sarcomas using RSF. This study aimed to determine associations between radiomic features and overall survival (OS) by RSF analysis. To identify radiomic features with important values by RSF analysis, construct predictive models for OS incorporating clinical characteristics, and evaluate models' performance with different method. We collected clinical characteristics and radiomic features extracted from plain and contrast-enhanced computed tomography (CT) from 353 patients with extremity and trunk wall soft-tissue sarcomas treated with surgical resection. All radiomic features were analyzed by Cox proportional hazard (CPH) and followed RSF analysis. The association between radiomics-predicted risks and OS was assessed by Kaplan-Meier analysis. All clinical features were screened by CPH analysis. Prognostic clinical and radiomic parameters were fitted into RSF and CPH integrative models for OS in the training cohort, respectively. The concordance indexes (C-index) and Brier scores of both two models were evaluated in both training and testing cohorts. The model with better predictive performance was interpreted with nomogram and calibration plots. Among all 86 radiomic features, there were three variables selected with high importance values. The RSF on these three features distinguished patients with high predicted risks from patients with low predicted risks for OS in the training set (P < 0.001) using Kaplan-Meier analysis. Age, lymph node involvement and grade were incorporated into the combined models for OS (P < 0.05). The C-indexes in both two integrative models fluctuated above 0.80 whose Brier scores maintained less than 15.0 in the training and testing datasets. The RSF model performed little advantages over the CPH model that the calibration curve of the RSF model showed favorable agreement between predicted and actual survival probabilities for the 3-year and 5-year survival prediction. The multimodality RSF model including clinical and radiomic characteristics conducted high capacity in prediction of OS which might assist individualized therapeutic regimens. Level III, prognostic study.

ASO Author Reflections: Reexcision after Macroscopically Complete Unplanned Excision in Extremity and Trunk Wall Soft Tissue Sarcoma: Is Less More?

ASO Author Reflections: Reexcision after Macroscopically Complete Unplanned Excision in Extremity and Trunk Wall Soft Tissue Sarcoma: Is Less More?

Unplanned Excision of Extremity and Trunk Wall Soft Tissue Sarcoma: To Re-resect or Not to Re-resect?

The need for systematic reexcision in patients who underwent unplanned excision (UE) for extremity and superficial trunk soft tissue sarcoma (ESTSTS) has been questioned. We investigated the outcome of patients who underwent reexcision for ESTSTS compared with primarily resected at our institution and the prognostic impact of microscopic residual disease (MR) in the reexcision specimen. Primary ESTSTS patients surgically treated at our institution between 1997 and 2017 were divided in three groups: primarily resected (A), reexcised after macroscopically complete UE (B), and incomplete UE (C). Weighted overall survival (OS), crude cumulative incidence of local relapse (CCI-LR), and distant metastasis (CCI-DM) were calculated and compared. In group B, multivariable models were performed to assess factors associated with the outcomes. A total of 1962 patients were identified: 1076,697 and 189 in groups A, B, and C, respectively. Overall median follow-up was 85 months. Seven-year weighted-OS was 73.8%, 84.1%, and 80.7% (p < 0.001) for groups A, B, and C respectively. Seven-year CCI-LR and DM were 5.0% and 25.3%, 12.1% and 15.8%, and 13.6% and 29.4% (both p < 0.001) for groups A, B, and C, respectively. At multivariable analysis, the presence MR was associated with LR (p < 0.001) but not with OS nor CCI-DM. UE and the presence of MR at pathology in reexcision specimen are associated to a higher risk of LR but not to a higher risk of DM or lower OS. After macroscopic complete UE, postponing reexcision until a LR occurs may be considered on an individualized basis.

1672PD - Improved survival with secondary surgery in a reference center after a first R1 or R2 resection in soft tissue sarcoma (STS) of the limbs or trunk wall: An analysis 10931 patients (pts) in NETSARC

BackgroundWe investigated the impact of secondary surgery (2Surg) after a first R1 or R2 resection in the 10931 pts with STS of the limb or trunk wall included in the nationwide NETSARC database from 2010 to 2017. MethodsNETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor boards (MDT), funded by the French NCI (INCa). Since 2010, presentation to an MDTB and second pathological review are mandatory for sarcoma pts. Statistics were performed with SPSS23.0. LRFS, metastasis-free survival (MFS), OS compared with the logrank test. ResultsIn 5295 (49.4%) patients, sarcoma were located on the lower limb, 3670 (33.6%) on trunk wall, 1966 (18.0%) on upper limb. Local RFS (LRFS) and RFS (p<0.001), but not OS, were superior for pts operated in a NETSARC center (N=4417, 41%). LRFS & OS were best for pts presented to a Netsarc MDT (NMDT) AND who were first operated in NETSARC centers; while the worst LRFS & OS were observed in pts presented in a NMDT but first operated outside a NetSARC center (p<0.001). Among the 2081 pts with a first R1 resection in whom 2Surg was documented, 1047 (50.3%) were reoperated. These R1 reoperated pts had a superior LRFS, metastatic free survival (MFS) and OS (p<0.001): LRFS (p<0.001), MFS (p=0.05) and OS (p<0.001) were superior after 2Surg only in pts operated 1st outside a Netsarc center. There were 823 pts with a first surgery with R2 resection in whom 2Surg was documented: 619 (75.2%) were reoperated. R2 reoperated patients had a superior LRFS and OS (p=0.01). MFS was not different. Again, LRFS (p<0.001) & OS (p<0.001) were superior after 2Surg only in pts operated 1st outside a Netsarc center. Among reoperated pts, those for whom 2Surg was in a NetSARC center had a superior LRFS & RFS (p<0.001) and OS (p=0.05). ConclusionsIn this nationwide series of limb or trunk wall STS, 2Surg after a R1 or R2 primary excision was associated with an improved OS only when pts had been operated first outside a reference center. 2Surg in a NETSARC center was associated with a better OS. Legal entity responsible for the studyJean-Yves Blay. FundingINCA (NetSarc, RREPS, RESOS, LYRICAN (INCA-DGOS-INSERM 12563), ARC fundation, Ligue de L’Ain contre le Cancer, INCA (NetSARC, RREPS, RESOS and LYRICAN (INCA-DGOS-INSERM 12563), InterSARC), La Ligue contre le Cancer, Ligue de L’Ain contre le Cancer, la Fondation ARC, EURACAN (EC 739521). DisclosureAll authors have declared no conflicts of interest.

Improved local relapse-free and overall survival with secondary surgery after a first R1 or R2 resection in soft tissue sarcoma (STS) of the limbs or trunk wall: An analysis 10,931 patients (pts) in NETSARC.

11056 Background: We previously reported that secondary resection (2Surg) improved local relapse free (LRFS) but not overall survival (OS) in a retrospective series of pts with localized STS after unplanned 1st excision. Here we investigated the impact of 2Surg specifically after a first R1 or R2 resection in the 10931 pts with STS of the limb or trunk wall included in the nationwide NETSARC database from 2010 to 2017. Methods: NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor boards (MDT), funded by the French NCI (INCa). Since 2010, presentation to an MDTB and second pathological review are mandatory for sarcoma pts. Statistics were performed with SPSS23.0. LRFS, metastasis-free survival (MFS), OS compared with the logrank test. Results: The series included 5598 (51.2%) males. Median age was 56.7. Tumor sites: 5295 (49.4%) lower limb, 3670 (33.6%) trunk wall. 1966 (18.0%) upper limb. As previously reported in the entire series, local RFS (LRFS) and RFS (p&lt;0.001), but not OS, were superior for pts presented to a NETSARC MDT (NMDT), or operated in a NETSARC center (N=4417, 41%). LRFS &amp; OS were best for pts presented to a NMDT AND operated in NETSARC centers; while the worst LRFS &amp; OS were observed in pts presented in a NMDT but not operated there (p&lt;0.001). Among the 2081 pts with a first R1 resection in whom 2Surg was documented, 1047 (50.3%) were reoperated. R1 reoperated pts had a superior LRFS, metastatic free survival (MFS) and OS (p&lt;0.001). LRFS (p&lt;0.001), MFS (p=0.05) and OS (p&lt;0.001) were superior after 2Surg only in pts operated 1st outside a Netsarc center. There were 823 pts with a first surgery with R2 resection in whom 2Surg was documented: 619 (75.2%) were reoperated. R2 reoperated patients had a superior LRFS and OS (p=0.01). MFS was not different. LRFS (p&lt;0.001) &amp; OS (p&lt;0.001) were superior after 2Surg only in pts operated 1st outside a Netsarc center. 2028 (%) pts had 2Surg. Pts for whom 2Surg was in a NetSARC center had a superior LRFS (p&lt;0.001) and OS (p=0.01) when operated first outside a NETSARC center. Conclusions: In this nationwide series of limb or trunk wall STS, 2Surg after a R1 or R2 primary excision improves LRFS &amp; OS when the pts were operated 1st outside a reference center. 2Surg in a NETSARC center was associated with a better LRFS and OS.

The impact of chemotherapy on survival of patients with extremity and trunk wall soft tissue sarcoma: revisiting the results of the EORTC-STBSG 62931 randomised trial

BackgroundThis study was aimed at determining whether patients with high-risk soft tissue sarcoma (STS), as identified using the nomogram Sarculator, benefitted from adjuvant chemotherapy in the EORTC-STBSG 62931 randomised controlled trial (RCT), which failed to detect an impact for adjuvant doxorubicin plus ifosfamide (Adj) over observation (Obs). MethodsPatients with extremity and trunk wall STS in the EORTC-STBSG 62931 RCT were analysed (N = 290/351). Ten-year predicted probability of overall survival (pr-OS) was calculated using the prognostic nomogram Sarculator. Patients were grouped into three categories of predicted pr-OS: high (pr-OS>66%), intermediate (51<pr-OS≤66) and low (pr-OS≤51%). OS and disease-free survival (DFS) were calculated. ResultsNomogram pr-OS was dispersed (median 72%, interquartile range 57–83%) and had prognostic value for OS and DFS (log-rank test: P < 0.001). One hundred seventy, 68 and 52 patients had high (58.6%, 90 Obs/80 Adj), intermediate (23.5%, 34 Obs/34 Adj) and low pr-OS (17.9%, 24 Obs/28 Adj), respectively. Adjuvant chemotherapy halved the risk of recurrence (hazard ratio [HR] = 0.46, 95% confidence interval [CI] 0.24–0.89) and death (HR = 0.46, 95% CI 0.23–0.94) in the low pr-OS category, while no effect was detected in intermediate and high pr-OS categories. To strengthen these findings, study participants with pr-OS<60% were combined (N = 80, 27.6%, 39 Obs/41 Adj), and a significant DFS (HR = 0.49, 95% CI 0.28–0.85) and OS (HR = 0.50, 95% CI 0.30–0.90) benefit was detected. ConclusionPatients of the EORTC-STBSG 62931 RCT with extremity and trunk wall STS and a low predicted pr-OS (high-risk patients) had better outcomes when treated with adjuvant chemotherapy. This may help reconcile the disparate results of clinical studies on adjuvant/neoadjuvant chemotherapy in STS.

Exploratory Dosimetric Study of the Impact of the Pre-Radiation Therapy Intra Tumoral Injection of Hafnium Oxide Nanoparticles Along the Radiation Treatment of Extremity and Trunk Wall Soft Tissue Sarcomas

Exploratory Dosimetric Study of the Impact of the Pre-Radiation Therapy Intra Tumoral Injection of Hafnium Oxide Nanoparticles Along the Radiation Treatment of Extremity and Trunk Wall Soft Tissue Sarcomas

The sarculator predicted risk of distant metastasis and overall survival in patients with high-risk soft tissue sarcoma treated with perioperative chemotherapy in a randomised controlled trial

Patients with high-risk extremity and trunk wall soft tissue sarcoma (STS, i.e. high malignancy grade and size > 5cm) have a wide survival range depending on histologic subtype and size. The Sarculator is a freely online-available accurate prognostic nomogram for patients with STS that improves current prognostic staging. We tested this tool for stratifying incidence of distant metastasis (DM) and overall survival (OS) rates in patients with high-risk STS enrolled in a randomised controlled trial (RCT) investigating neoadjuvant/adjuvant chemotherapy.

The Impact of Chemotherapy on Survival of Patients with Extremity and Trunk Wall Soft Tissue Sarcoma: Revisiting the Results of the EORTC-STBSG 62931 Randomised Trial Using Sarculator, a Validated Nomogram-Based Risk Assessment Tool

BACKGROUND: To determine whether patients with high-risk soft tissue sarcoma (STS), as identified using the nomogram Sarculator, benefitted from adjuvant chemotherapy in the EORTC-STBSG 62931 randomised controlled trial (RCT) which failed to detect an impact for adjuvant doxorubicin plus ifosfamide (Adj) over observation (Obs). METHODS: A retrospective analysis of the EORTC-STBSG 62931 RCT was performed on individual patient data of study participants with extremity and trunk wall STS (N=290/351). 10-year predicted probability of overall survival (pr-OS) was calculated using the prognostic nomogram Sarculator. Patients were grouped in three categories of predicted pr-OS: high (pr-OS > 66%), intermediate (51< pr-OS ≤ 66), and low (pr-OS ≤ 51%). OS and disease-free survival (DFS) were calculated at the study median follow-up (8-year). FINDINGS: Nomogram pr-OS were dispersed (median 72%, IQR 57-83%) and had prognostic value for OS and DFS (Log-Rank test: P<0·001). 170 patients had high pr-OS (58·6%, 90 Obs/80 Adj), 68 intermediate (23·5%, 34 Obs/34 Adj) and 52 low (17·9%, 24 Obs/28 Adj). Adjuvant chemotherapy halved the risk of recurrence (HR=0·46, 95%CI 0·24-0·89) and death (HR=0·46, 95%CI 0·23-0·94) in the low pr-OS category, while no effect was detected in the intermediate and high pr-OS categories. In order to strengthen these findings, study participants with predicted pr-OS<60% were combined (N=80, 27·6%, 39 Obs/41 Adj) and a significant benefit in terms of DFS (HR=0·49, 95%CI 0·28-0·85) and OS (HR=0·50, 95%CI 0·30-0·90) was detected. INTERPRETATION: Patients of the EORTC-STBSG 62931 RCT with extremity and trunk wall STS and a low predicted pr-OS (i.e., high-risk patients) had a better outcome when treated with adjuvant chemotherapy. This may help reconcile the somewhat disparate results of published clinical studies on adjuvant/neoadjuvant chemotherapy in high/risk STS. Funding Statement: This was an academic non-funded study. The EORTC-STBSG 62931 trial was funded by European Organisation for Research and Treatment of Cancer (EORTC) and Rhone-Poulenc-Rorer. Declaration of Interests: The authors declare they have no conflicts of interest. Ethics Approval Statement: The protocol of the EORTC-STBSG 62931study was approved by the EORTC Protocol Review Committee and institutional review boards. The patients gave informed consent according to applicable laws in all participating countries. The current study was approved by EORTC through the ‘Request for data platform’.

High-risk soft tissue sarcomas treated with perioperative chemotherapy: Improving prognostic classification in a randomised clinical trial

BackgroundPatients with extremity and trunk wall soft tissue sarcoma (STS) with high malignancy grade and size >5 cm are at high-risk of death. This risk varies depending also on other patient and tumour features, including histologic subtype. This study investigated whether a prognostic nomogram can improve risk assessment of these patients. MethodsData from high-risk STS patients enrolled in a randomised controlled trial investigating different perioperative chemotherapy regimens were analysed. Ten-year probability of overall survival (OS) and incidence of distant metastasis (DM) were computed using the prognostic nomogram Sarculator (pr-OS and inc-DM, respectively). Tumour response according to RECIST and Choi criteria was also investigated. FindingsVariation in pr-OS and inc-DM were observed and patients stratified in three prognostic groups. The 10-year OS in the low, intermediate, and high pr-OS categories were 0·42 (95%CI 0·32–0·52), 0·63 (95%CI 0·53–0·72), and 0·78 (95%CI 0·68–0·85), respectively. Patients in the intermediate (HR 0·51, P = 0·002) and high (HR 0·28, P < 0·001) pr-OS categories were at statistically significant lower risk of death compared with those in the low pr-OS category. Higher rate of Choi partial tumour responses were detected in intermediate pr-OS category. Tumour response according to Choi but not to RECIST criteria stratified patient survival of pr-OS categories, particularly for patients with intermediate to low pr-OS. Analyses conducted for 10-year inc-DM were consistent with results for pr-OS for prognostic value of Sarculator predictions and Choi tumour response. InterpretationSarculator identifies variations in outcomes of high-risk STS treated with perioperative chemotherapy and improve prognostic classification, which is also associated with different patterns of tumour response, an outcome that further stratifies survival particularly for patients predicted at higher risk. Future trials investigating neoadjuvant chemotherapy should consider prognostic tool for selecting patients to be enrolled. Trial registration numberEuropean Union Drug Regulating Authorities Clinical Trials No. 2004-003979-36.

Neoadjuvant chemotherapy in localised soft-tissue sarcomas: where do we go from here?

In The Lancet Oncology, Alessandro Gronchi and colleagues report a phase 3 trial 1 Gronchi A Ferrari S Quagliuolo V et al. Histotype-tailored neoadjuvant chemotherapy versus standard chemotherapy in patients with high-risk soft-tissue sarcomas (ISG-STS 1001): an international, open-label, randomised, controlled, phase 3, multicentre trial. Lancet Oncol. 2017; 18: 812-822 Summary Full Text Full Text PDF PubMed Scopus (292) Google Scholar randomly assigning 287 patients with localised, high-risk extremity and trunk wall soft-tissue sarcomas to receive three cycles of histotype-tailored chemotherapy versus a standard control of full-dose chemotherapy with epirubicin plus ifosfamide. With a median follow-up of 12·3 months (IQR 2·75–28·20), the trial was closed prematurely after the third interim analysis for futility because superiority for the histotype-tailored chemotherapy group was not to be expected for both the primary endpoint disease-free survival and the secondary endpoint overall survival. Histotype-tailored neoadjuvant chemotherapy versus standard chemotherapy in patients with high-risk soft-tissue sarcomas (ISG-STS 1001): an international, open-label, randomised, controlled, phase 3, multicentre trialIn a population of patients with high-risk soft-tissue sarcoma, we did not show any benefit of a neoadjuvant histotype-tailored chemotherapy regimen over the standard chemotherapy regimen. The benefit seen with the standard chemotherapy regimen suggests that this benefit might be the added value of neoadjuvant chemotherapy itself in patients with high-risk soft-tissue sarcoma. Full-Text PDF

The sarculator stratified prognosis of patients with high-risk soft tissue sarcomas (STS) of extremities and trunk wall treated with perioperative chemotherapy in a randomised controlled trial (RCT).

11016 Background: Patients with extremity and trunk wall STS with high malignancy grade and size larger than 5cm are considered at high risk of death, but in fact this risk varies broadly depending on histologic subtype and size. The Sarculator, a nomogram for STS, can improve prognostic assessment of these patients. This tool was evaluated for stratifying risk of distant metastasis (DM) and overall survival (OS) in a RCT investigating perioperative chemotherapy. Methods: High-risk STS patients were randomly assigned to receive either three cycles of preoperative chemotherapy with epirubicin (120 mg/m2) and ifosfamide (9 g/m2) or the same three preoperative cycles followed by two further postoperative cycles. The Sarculator was used to stratify patient risk according to predicted 10-year cumulative incidence of DM and OS rates. Results: The Sarculator identified three different prognostic groups of patients at low (N = 101), intermediate (N = 102), and high (N = 107) risk. Cumulative incidence of DM was 0.26 (SE: 0.04), 0.31 (SE: 0.05), and 0.48 (SE: 0.05) for low, intermediate, and high risk patients, respectively. Similarly, OS rates were 0.78 (95%CI 0.68-0.85), 0.63 (95%CI 0.53-0.72), and 0.42 (95%CI 0.32-0.52), respectively. Patients in the low risk group were at significantly lower risk of death compared to those in the intermediate (HR 0.51, 95%CI 0.34-0.78, P = 0.002) and high (HR 0.28, 95%CI 0.17-0.46, P &lt; 0.001) risk groups. Subgroup analysis performed by jointly considering these three groups and the two study arms did not identify statistically significant survival differences between the treatment arms within each risk category. Conclusions: Patients with high-risk STS included in this RCT were not a homogeneous population. The Sarculator identified different risk groups for DM and OS even in patients included in a RCT investigating perioperative treatments. This tool should be considered for redefining high-risk STS and stratifying patient risk in future RCT investigating perioperative chemotherapy. Clinical trial information: 2004-003979-36.

The Scandinavian Sarcoma Group Central Register: 6,000 patients after 25 years of monitoring of referral and treatment of extremity and trunk wall soft-tissue sarcoma

Purpose — We wanted to examine the potential of the Scandinavian Sarcoma Group (SSG) Central Register, and evaluate referral and treatment practice for soft-tissue sarcomas in the extremities and trunk wall (STS) in the Nordic countries.Background — Based on incidence rates from the literature, 8,150 (7,000–9,300) cases of STS of the extremity and trunk wall should have been diagnosed in Norway, Finland, Iceland, and Sweden from 1987 through 2011. The SSG Register has 6,027 cases registered from this period, with 5,837 having complete registration of key variables. 10 centers have been reporting to the Register. The 5 centers that consistently report treat approximately 90% of the cases in their respective regions. The remaining centers have reported all the patients who were treated during certain time periods, but not for the entire 25-year period.Results — 59% of patients were referred to a sarcoma center untouched, i.e. before any attempt at open biopsy. There was an improvement from 52% during the first 5 years to 70% during the last 5 years. 50% had wide or better margins at surgery. Wide margins are now achieved less often than 20 years ago, in parallel with an increase in the use of radiotherapy. For the centers that consistently report, 97% of surviving patients are followed for more than 4 years. Metastasis-free survival (MFS) increased from 67% to 73% during the 25-year period.Interpretation — The Register is considered to be representative of extremity and trunk wall sarcoma disease in the population of Scandinavia, treated at the reporting centers. There were no clinically significant differences in treatment results at these centers.

The risk of postoperative complications and functional impairment after multimodality treatment for limb and trunk wall soft-tissue sarcoma: Long term results from a monocentric series

Background and objectivesConservative surgery for soft-tissue sarcoma (STS) within multimodality treatment attempts to reconcile two contradictory requirements: assuring a good oncological outcome through a wide resection and preserving the function. The aim of our study is to verify whether our conservative approach to STS met these objectives. MethodsA retrospective database analysis was performed in adults with primary limb or trunk wall STS operated in a single center from 1989 to 2012. Predictive factors for postoperative complications and functional impairment were tested in a multivariate analysis. Results728 patients were operated (resection R0: 68%). Neoadjuvant chemotherapy (NAC) was given to 28%, postoperative radiotherapy to 70% of patients. Median follow-up was 103 months. At five years, overall survival was 80% and local recurrences 11%. Major postoperative complications occurred in 8% and functional impairment in 13% of the patients. Independent predictive factors for postoperative complications were American Society of Anesthesiologist classes 2 and 3 (OR: 2.3, CI: 1.2–4.5 and 4.0 CI: 1.7–9.3), tumor size >80 mm (OR: 2.5, CI: 1.3–4.9), tumor site (trunk wall/lower limb, OR: 4.1, CI: 1.3–13.6) and multifocal/multicompartmental spread (OR: 2, CI: 1.1–3.6). Independent predictive factors for function impairment were postoperative complications (OR: 5.3, CI: 2.8–10.1), NAC (OR: 3.6, CI: 2.2–5.8), and bone or neurovascular involvement (OR 3.3, CI 2.0–5.3), whereas Early Rehabilitation after Surgery (ERAS) improved outcome (OR: 0.5, CI: 0.3–0.9). ConclusionPostoperative complications induced functional impairment. They may be reduced by acting on comorbidity factors and careful tumor evaluation prior to surgery. Furthermore, ERAS measures improved function.

Time interval between surgery and start of adjuvant radiotherapy in patients with soft tissue sarcoma: A retrospective analysis of 1131 cases from the French Sarcoma Group

PurposeThe aim of this study was to evaluate the impact of the time interval (TI) between surgery and adjuvant radiotherapy (RT) in soft tissue sarcoma (STS). Methods and materialsData from 1131 patients treated between 1990 and 2014 were retrospectively reviewed. Inclusion criteria were: limb or superficial trunk wall STS (R0 or R1 resection) and adjuvant RT. The impact of TI on 10-year local relapse-free survival (LRFS) and 10-year overall survival (OS) was analyzed using a Log-rank test and then Cox Model. ResultsThe median TI was 82days (range, 18–346). With a median follow-up of 235months (range, 2–296months), the 10-year LRFS was 57.5% (±2%) and the 10-year OS was 64.2% (±2%). With a TI of 19–39days, 40–79days, 80–119days, and ⩾120days, 10-year LRFSs were 65.3%, 55.5%, 56.9% and 61.2% (p=0.465), and 10-year OSs were 72.8%, 60.7%, 66.4% and 62.1% (p=0.347), respectively. After adjustment for the factors significantly (p⩽0.05) associated with LRFS and OS, TI did not alter LRFS (p=0.182) either OS (p=0.335). ConclusionsIn this retrospective STS database study, the TI between surgery and start of adjuvant RT did not seem to affect outcomes.

The introduction of early patient rehabilitation in surgery of soft tissue sarcoma and its impact on post-operative outcome

BackgroundEnhanced recovery after surgery (ERAS) programs are implemented in multiple fields of surgery, but not yet in soft-tissue sarcoma (STS) surgery. We wondered whether its introduction into STS surgery might have impacted postoperative outcome. MethodsTwo hundred and fifty seven adult patients with primary limb or trunk wall STS received ERAS from 2008 to 2012 as a part of the intra-operative management. We evaluated, in retrospect, the intra-operative management, post-operative outcomes, functional and oncological results of these patients and compared them with 459 prior patients treated under a standard recovery after surgery (SRAS) program from 1989 to 2007. ResultsThe most visible change from SRAS to ERAS in the perioperative management was decrease of wound drainage (72% vs. 15%, p < 0.001) and increase of wound bandaging (16% vs. 66%; p < 0.001), underlining the appliance of the ERAS protocol. Post-operatively, hospital stay dropped from nine (0–74) to three (0–22) days (p < 0.001) without affecting major morbidity (8% vs. 5%, NS) or readmission to the hospital (5% vs. 4%, NS). Functional outcome improved (p = 0.009) but whether this change was due to ERAS remains to be proved because complementary treatments changed over time. Tumour control remained unaffected, with an estimated risk of local recurrence at 5 years of 12% in both groups. ConclusionIntroducing a rapid recovery program was associated with a shorter hospitalization stay without compromising surgical or oncological outcomes. The program appears to be safe and reliable to use in patients undergoing STS surgery.