scholarly journals Immunologic constant of rejection signature is prognostic in soft-tissue sarcoma and refines the CINSARC signature

2022 ◽  
Vol 10 (1) ◽  
pp. e003687
Author(s):  
Francois Bertucci ◽  
Vincent Niziers ◽  
Alexandre de Nonneville ◽  
Pascal Finetti ◽  
Léna Mescam ◽  
...  
Keyword(s):  
Immune Response ◽  
Soft Tissue ◽  
Early Stage ◽  
Soft Tissue Sarcomas ◽  
Independent Set ◽  
Prognostic Features ◽  
Biological Variables ◽  
Pathological Type ◽  
Increased Risk ◽  
Metastatic Relapse

BackgroundSoft-tissue sarcomas (STSs) are heterogeneous and aggressive tumors, with high metastatic risk. The immunologic constant of rejection (ICR) 20-gene signature is a signature of cytotoxic immune response. We hypothesized that ICR might improve the prognostic assessment of early-stage STS.MethodsWe retrospectively applied ICR to 1455 non-metastatic STS and searched for correlations between ICR classes and clinicopathological and biological variables, including metastasis-free survival (MFS).ResultsThirty-four per cent of tumors were classified as ICR1, 27% ICR2, 24% ICR3, and 15% ICR4. These classes were associated with patients’ age, pathological type, and tumor depth, and an enrichment from ICR1 to ICR4 of quantitative/qualitative scores of immune response. ICR1 class was associated with a 59% increased risk of metastatic relapse when compared with ICR2-4 class. In multivariate analysis, ICR classification remained associated with MFS, as well as pathological type and Complexity Index in Sarcomas (CINSARC) classification, suggesting independent prognostic value. A prognostic clinicogenomic model, including the three variables, was built in a learning set (n=339) and validated in an independent set (n=339), showing greater prognostic precision than each variable alone or in doublet. Finally, connectivity mapping analysis identified drug classes potentially able to reverse the expression profile of poor-prognosis tumors, such as chemotherapy and targeted therapies.ConclusionICR signature is independently associated with postoperative MFS in early-stage STS, independently from other prognostic features, including CINSARC. We built a robust prognostic clinicogenomic model integrating ICR, CINSARC, and pathological type, and suggested differential vulnerability of each prognostic group to different systemic therapies.

scholarly journals Improving Immunotherapy Efficacy in Soft-Tissue Sarcomas: A Biomarker Driven and Histotype Tailored Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Matthieu Roulleaux Dugage ◽  
Elise F. Nassif ◽  
Antoine Italiano ◽  
Rastislav Bahleda
Keyword(s):  
Soft Tissue ◽  
Immune Checkpoint ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Early Stage ◽  
Soft Tissue Sarcomas ◽  
Oncolytic Viruses ◽  
Cellular Therapies ◽  
M1 Macrophage ◽  
Synovial Sarcomas

Anti-PD-(L)1 therapies yield a disappointing response rate of 15% across soft-tissue sarcomas, even if some subtypes benefit more than others. The proportions of TAMs and TILs in their tumor microenvironment are variable, and this heterogeneity correlates to histotype. Tumors with a richer CD8+ T cell, M1 macrophage, and CD20+ cells infiltrate have a better prognosis than those infiltrated by M0/M2 macrophages and a high immune checkpoint protein expression. PD-L1 and CD8+ infiltrate seem correlated to response to immune checkpoint inhibitors (ICI), but tertiary lymphoid structures have the best predictive value and have been validated prospectively. Trials for combination therapies are ongoing and focus on the association of ICI with chemotherapy, achieving encouraging results especially with pembrolizumab and doxorubicin at an early stage, or ICI with antiangiogenics. A synergy with oncolytic viruses is seen and intratumoral talimogene laherpavec yields an impressive 35% ORR when associated to pembrolizumab. Adoptive cellular therapies are also of great interest in tumors with a high expression of cancer-testis antigens (CTA), such as synovial sarcomas or myxoid round cell liposarcomas with an ORR ranging from 20 to 50%. It seems crucial to adapt the design of clinical trials to histology. Leiomyosarcomas are characterized by complex genomics but are poorly infiltrated by immune cells and do not benefit from ICI. They should be tested with PIK3CA/AKT inhibition, IDO blockade, or treatments aiming at increasing antigenicity (radiotherapy, PARP inhibitors). DDLPS are more infiltrated and have higher PD-L1 expression, but responses to ICI remain variable across clinical studies. Combinations with MDM2 antagonists or CDK4/6 inhibitors may improve responses for DDLPS. UPS harbor the highest copy number alterations (CNA) and mutation rates, with a rich immune infiltrate containing TLS. They have a promising 15-40% ORR to ICI. Trials for ICB should focus on immune-high UPS. Association of ICI with FGFR inhibitors warrants further exploration in the immune-low group of UPS. Finally translocation-related sarcomas are heterogeneous, and although synovial sarcomas a poorly infiltrated and have a poor response rate to ICI, ASPS largely benefit from ICB monotherapy or its association with antiangiogenics agents. Targeting specific neoantigens through vaccine or adoptive cellular therapies is probably the most promising approach in synovial sarcomas.

Sarcomas of Soft Tissue and Bone

2011 ◽  
Author(s):  
Adam Lerner ◽  
Huihong Xu ◽  
Karen H Antman
Keyword(s):  
Soft Tissue ◽  
Meta Analysis ◽  
Survival Rates ◽  
Fibrous Tissue ◽  
Soft Tissue Sarcomas ◽  
Kaposi Sarcoma ◽  
Uterine Leiomyosarcoma ◽  
Increased Risk ◽  
Bone Sarcomas ◽  
Epidemiologic Features

Sarcomas originate from bone or soft tissue. The most common bone sarcomas are osteosarcomas, Ewing sarcomas, and chondrosarcomas. Soft tissue sarcomas develop in fibrous tissue, fat, muscle, blood vessels, and nerves. Historically, soft tissue sarcomas of the trunk and extremities were reported separately from those of visceral organs (e.g., gastrointestinal and gynecologic sarcomas). This chapter discusses the classification, epidemiology, diagnosis, staging, and treatment of sarcomas of bone and cartilage, and classic soft tissue sarcomas. Management of Kaposi sarcoma, gastrointestinal stromal tumors (GISTs), mesothelioma, and rhabdomyosarcoma is also described. Figures include images of patients with osteosarcoma, liposarcoma, uterine leiomyosarcoma, GIST, and osteosarcoma in a patient with Paget disease of bone. Tables list epidemiologic features of sarcomas, a summary of sarcomas by histology, familial syndromes associated with increased risk of sarcoma, survival rates in sarcoma patients, staging of soft tissue sarcomas, and results of a meta-analysis of doxorubicin-based adjuvant chemotherapy for localized resectable soft tissue sarcoma. This chapter contains 126 references.

Epidemiology of patients with musculoskeletal soft tissue sarcomas in a cancer hospital in Central China: A study of 1624 cases.

2020 ◽  
Author(s):  
Peng Zhang ◽  
Jinyan Liu ◽  
Feifei Feng ◽  
Qiao Zhang ◽  
Guangcai Duan ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Synovial Sarcoma ◽  
Soft Tissue Sarcomas ◽  
Tumor Location ◽  
Henan Province ◽  
Central China ◽  
Gender Ratio ◽  
Pathological Type ◽  
Cancer Hospital ◽  
Pathological Subtypes

Abstract Background : To analyze the incidence characteristics of 1624 inpatients with soft tissue sarcoma (STS) during 2006 to 2016 in Henan Province Cancer Hospital in Central China. Methods : The information of electronic medical record from the first hospitalized patients with STS in Henan Province Cancer Hospital during January 1, 2006 to December 31, 2016 was collected, and descriptive statistics was analyzed on age, gender, pathological type and tumor location by using SPSS21.0 software. Results : There were 1624 inpatients with STS in Henan Province Cancer Hospital in 2006~2016.The top nine pathological subtypes of STS with high constituent ratio were undifferentiated pleomorphic sarcoma (UPS,23.83%),synovial sarcoma(16.69%), liposarcoma(13.67%), fibrosarcoma(10.22%), sarcoma without definite type (8.99%), leiomyosarcoma(7.02%), dermatofibrosarcoma protuberant (5.79%),rhabdomyosarcoma (4.68%) and malignant neurilemmoma(4.25%). The average age of inpatients was 44.71±17.91, and the inpatients aged 35-64 accounted for 56.34%.The number of UPS inpatients reached the peak at the age of 45 to 59; The median age of inpatients with rhabdomyosarcoma was 17 year.In total 1624 inpatients of STS, the number of male and female inpatients were 923 and 701, respectively. The gender ratio was 1.32:1. The proportion of UPS in either male or female inpatients was the highest, accounting for 23.07% and 24.82%, respectively. The number of male inpatients was more than that of female in the top nine pathological subtypes of STS except leiomyosarcoma (the gender ratio was 0.84:1). The most common initiation location of UPS, synovial sarcoma, liposarcoma was lower extremity, accounting for 51.16%, 53.13% and 52.25% in corresponding pathological type group, respectively. Dermatofibrosarcoma protuberant, rhabdomyosarcoma and fibrosarcoma were all mainly initiated in trunk, accounting for 72.34%, 47.83% and 45.57% , respectively. Leiomyosarcoma tend to occur in retroperitoneum. Conclusion : The top three pathological subtypes of STS with high constituent ratio were UPS, synovial sarcoma and liposarcoma.UPS should be paid more attention on the prevention, treatment and research in Henan province in future for its highest proportion of STS.

scholarly journals Focus on the Tumour Periphery in MRI Evaluation of Soft Tissue Sarcoma: Infiltrative Growth Signifies Poor Prognosis

Sarcoma ◽  
2006 ◽  
Vol 2006 ◽  
pp. 1-5 ◽  
Author(s):  
Josefin Fernebro ◽  
Marie Wiklund ◽  
Kjell Jonsson ◽  
Pär-Ola Bendahl ◽  
Anders Rydholm ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Growth Pattern ◽  
Tumour Growth ◽  
Neoadjuvant Treatment ◽  
Soft Tissue Sarcomas ◽  
Prognostic Information ◽  
Diffuse Infiltration ◽  
Increased Risk ◽  
Tumour Periphery ◽  
Mri Evaluation

Purpose. Infiltrative microscopical peripheral growth of soft tissue sarcomas (STS) has been shown to be of prognostic importance and preoperative risk stratification could individualize neoadjuvant treatment.Patients and methods. We assessed peripheral tumour growth pattern on preoperative MRI from 78 STS. The findings were correlated to histopathology and to outcome.Results. The MRI-based peripheral tumour growth pattern was classified as pushing in 34 tumours, focally infiltrative in 25, and diffusely infiltrative in 19. All tumours with diffuse infiltration on MRI also showed microscopical infiltration, whereas MRI failed to identify infiltration in two-thirds of the microscopically infiltrative tumours. Diffusely infiltrative growth on MRI gave a 2.5 times increased risk of metastases (P=.01) and a 3.7 times higher risk of local recurrence (P=.02).Discussion. Based on this observation we suggest that MRI evaluation of STS should focus on the peripheral tumour growth pattern since it adds prognostic information of value for decisions on neoadjuvant therapies.

scholarly journals Prognostic Factors in Extremity Soft Tissue Sarcoma Patients Treated with Preoperative Radiotherapy

2019 ◽  
Vol 4 (03) ◽  
Author(s):  
Berrin Inanc, MD ◽  
Kubilay Inanc, MD
Keyword(s):  
Prognostic Factors ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Preoperative Radiotherapy ◽  
Soft Tissue Sarcomas ◽  
Tumor Grade ◽  
Metastatic Recurrence ◽  
Extremity Soft Tissue Sarcoma ◽  
Metastatic Relapse

Purpose: The purpose of the study was to investigate the prognostic factors and survival after preoperative radiotherapy in Extremity Soft Tissue Sarcomas (ESTS). Materials and Methods: In this retrospective study, all patients treated for an extremity sarcoma with pre-operative radiotherapy followed by surgery. Results: The mean follow-up for all 24 ESTS patients was 15.5 (range: 10-39 months). At last follow-up, 9 patients (37%) were alive, 15 patients (62%) had died of distant disease progression. Among the patients died, there were 15 with metastatic relapse (13 lung and 2 cranial metastasis), 5 with both local and metastatic recurrence. The median OS was 16 month. The 2-years actuarial OS rate and 3-years OS rate were 39% and 26%, respectively. The median RFS was 14(12.5-15.4) month. The 2-years and 3-years RFS rate was 71%.The median MFS was 12 months. The 2-years and 3-years MFS rate were 33%, 17%, respectively. The effects of age, sex, histopathologic type, tumor size, tumor localization, tumor grade, tumor depth, radiation doses and recestion margin on OS, RFS, MFS were not observed. In univariate and multivariate model, it was observed that recurrence decreased OS time significantly (p<0.05). Conclusion: Recurrens and metastasis are strong and negative prognostic factor for survival in extremity soft tissue sarcoma patients.

Sarcomas of the Soft Tissue and Bone

2011 ◽  
Author(s):  
Adam Lerner ◽  
Huihong Xu ◽  
Karen H Antman
Keyword(s):  
Soft Tissue ◽  
Meta Analysis ◽  
Survival Rates ◽  
Fibrous Tissue ◽  
Soft Tissue Sarcomas ◽  
Kaposi Sarcoma ◽  
Uterine Leiomyosarcoma ◽  
Increased Risk ◽  
Bone Sarcomas ◽  
Epidemiologic Features

Sarcomas originate from bone or soft tissue. The most common bone sarcomas are osteosarcomas, Ewing sarcomas, and chondrosarcomas. Soft tissue sarcomas develop in fibrous tissue, fat, muscle, blood vessels, and nerves. Historically, soft tissue sarcomas of the trunk and extremities were reported separately from those of visceral organs (e.g., gastrointestinal and gynecologic sarcomas). This chapter discusses the classification, epidemiology, diagnosis, staging, and treatment of sarcomas of bone and cartilage, and classic soft tissue sarcomas. Management of Kaposi sarcoma, gastrointestinal stromal tumors (GISTs), mesothelioma, and rhabdomyosarcoma is also described. Figures include images of patients with osteosarcoma, liposarcoma, uterine leiomyosarcoma, GIST, and osteosarcoma in a patient with Paget disease of bone. Tables list epidemiologic features of sarcomas, a summary of sarcomas by histology, familial syndromes associated with increased risk of sarcoma, survival rates in sarcoma patients, staging of soft tissue sarcomas, and results of a meta-analysis of doxorubicin-based adjuvant chemotherapy for localized resectable soft tissue sarcoma. This chapter contains 126 references.

Implementing a Machine Learning Strategy to Predict Pathologic Response in Patients With Soft Tissue Sarcomas Treated With Neoadjuvant Chemotherapy

2021 ◽  
pp. 958-972
Author(s):  
Amandine Crombé ◽  
Sophie Cousin ◽  
Mariella Spalato-Ceruso ◽  
François Le Loarer ◽  
Maud Toulmonde ◽  
...  
Keyword(s):  
Machine Learning ◽  
Soft Tissue ◽  
Neoadjuvant Chemotherapy ◽  
Standard Model ◽  
Cox Regression ◽  
Soft Tissue Sarcomas ◽  
Histologic Response ◽  
Surgical Specimen ◽  
Metastatic Relapse ◽  
The Standard Model

PURPOSE Neoadjuvant chemotherapy (NAC) has been increasingly used in patients with locally advanced high-risk soft tissue sarcomas in the past decade, but definition and prognostic impact of a good histologic response (GHR) are lacking. Our aim was to investigate which histologic feature from the post-NAC surgical specimen independently correlated with metastatic relapse-free survival (MFS) in combination with clinical, radiologic, and pathologic features using a machine learning approach. METHODS This retrospective study included 175 consecutive patients (median age: 59 years, 75 women) with resectable disease, treated with anthracycline-based NAC between 1989 and 2015 in our sarcoma reference center, and with quantitative histopathologic analysis of the surgical specimen. The outcome of interest was the MFS. A multimodel, multivariate survival analysis was used to define GHR. The added prognostic value of GHR was investigated through the comparisons with the standard model (including histologic grade, size, and depth) and SARCULATOR nomogram using concordance indices (c-index) and Monte-Carlo cross-validation. RESULTS Seventy-two patients (72 of 175, 41.1%) had a metastatic relapse. Stepwise Cox regression, random survival forests, and least absolute shrinkage and selection operator–penalized Cox regression all converged toward the same definition for GHR, ie, < 5% stainable tumor cells. The five-year MFS probability was 1 (95% CI, 1 to 1) in patients with GHR versus 0.73 (95% CI, 0.65 to 0.81) in patients without GHR (log-rank P = .0122). The final prognostic model incorporating the GHR was significantly better than the standard model and SARCULATOR (average c-index in testing sets = 0.72 [95% CI, 0.61 to 0.82] v 0.57 [95% CI, 0.44 to 0.70] and 0.54 [95% CI, 0.45 to 0.64], respectively; P = .0414 and .0091). CONCLUSION Histologic response to NAC improves the prediction of MFS in patients with soft tissue sarcoma and represents a possible end point in future studies exploring innovative regimens in the neoadjuvant setting.

Incidence and predictive factors of late relapse in patients with soft tissue sarcomas: Implications for prolonged follow-up.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 10574-10574
Author(s):  
Maud Toulmonde ◽  
Axel Le Cesne ◽  
Jean Mendiboure ◽  
Jean-Yves Blay ◽  
Sophie Piperno-Neumann ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Soft Tissue ◽  
Univariate Analysis ◽  
Local Relapse ◽  
Late Relapse ◽  
Histological Subtype ◽  
Initial Management ◽  
Increased Risk ◽  
Metastatic Relapse

10574 Background: There is no consensus on how to follow soft-tissue sarcoma (STS) patients after their initial management. In particular, the incidence of late relapse which would justify prolonged surveillance is unknown. Methods: Follow-up data were reviewed from 719 patients with localized STS, included in the French Sarcoma Group database from January 1990 to June 2005, and who achieved complete remission maintained for at least five years after their initial management. The outcomes of interest were the cumulative probabilities of late (> 5 years) local and metastatic relapse with death as a competing event. Estimations and 95% confidence intervals (CIs) were computed with the cumulative incidence function. Patients who did not experience the event of interest or death over the course of the study were censored at their last follow-up. Results: 67 (9.3%) and 42 (5.8%) patients had late local and metastatic relapse respectively. On univariate analysis, internal trunk location, liposarcoma histological subtype, tumor size > 10 cm, R1 margins, no adjuvant radiotherapy were significantly associated with increased risk of late local relapse. On multivariate analysis, internal trunk location (HR= 3.9, 95% CI 2.2-6.7, p<0.001) and tumor size > 10 cm (HR= 2.1, 95% CI 1.1-4, p=0.03) were the two factors independently associated with local relapse. On univariate analysis, leiomyosarcoma histological subtype, and grade > 1 were significantly associated with increased risk of late metastatic relapse. On multivariate analysis, grade > 1 (HR= 4.7, 95% CI 1.1-21, p=0.04) was the sole factor independently associated with the risk of late metastatic relapse. Conclusions: Late relapse of STS (> 5 years after initial management) is relatively uncommon. However, its existence and our results emphasize the critical role of long-term follow-up to detect late local recurrence in patients with retroperitoneal or very large STS and late metastatic recurrence in patients with high grade disease.

Surgical Management and Minimally Invasive Approaches for the Treatment of Metastatic Sarcoma

2013 ◽  
pp. 457-464
Author(s):  
Peter Hohenberger ◽  
Bernd Kasper ◽  
Kamran Ahrar
Keyword(s):  
Soft Tissue ◽  
Minimally Invasive ◽  
Early Stage ◽  
Tumor Biology ◽  
Local Treatment ◽  
Soft Tissue Sarcomas ◽  
Metastatic Tumor ◽  
Soft Tissue Tumors ◽  
Tumor Spread ◽  
Systemic Treatments

Soft tissue sarcomas describe a very heterogeneous group of soft tissue tumors mainly arising in the lower extremities. If diagnosed at an early stage and a complete resection of the primary tumor is achieved, the patients' prognosis is excellent. However, metastatic tumor spread is common with only limited treatment possibilities. Despite an improved insight into tumor biology of sarcomas, no notable improvement has been gained in the last 20 years regarding prognosis of patients. Metastatic lung disease has long been the preserve of systemic treatments, local treatments being considered in a purely palliative intention. Several studies have objectified benefit to the local treatment of metastases, especially in an oligometastatic state. The development of techniques for stereotactic radiotherapy on the one hand and the refusal or contraindication for surgery on the other hand inaugurated studies in this direction. Besides surgery and radiotherapy, other local modalities have been investigated in the last few years such as thermal therapy (radiofrequency and laser ablation) or combined modalities (isolated limb perfusion and deep-wave hyperthermia plus chemotherapy) to help patients with metastatic soft tissue sarcoma. Minimally invasive, image-guided therapies such as thermal ablation should be considered particularly in patients who are not suitable surgical candidates or may have exhausted all other viable surgical options. Some of these techniques will be reviewed in this article, and their value for the patients will be evaluated in the light of indication from tumor biology and technical feasibility. These highly selected and specific procedures should only be performed after decision making in an interdisciplinary sarcoma-board.

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