Centres De Lutte Contre Le Research Articles

Comparing Apparent Diffusion Coefficient and FNCLCC Grading to Improve Pretreatment Grading of Soft Tissue Sarcoma-A Translational Feasibility Study on Fusion Imaging.

Simple SummaryHistological subtype and grading are essential for the planning of soft tissue sarcoma. Pretherapeutic grading based on core needle biopsies is frequently not reliable due to intratumoral heterogeneity. This pilot study assessed the ability of functional radiological imaging to improve histopathological grading. Multiple biopsies were taken from the sarcoma specimens during tumor resection and radiopaque markers were placed. Subsequently, fusion of preoperative magnetic resonance imaging and postoperative computed tomography of the specimen allowed for comparison of histopathological grading and diffusion-weighted imaging. The apparent diffusion coefficient appears to correlate with FNCLCC criteria and may supplement pretreatment assessment and multimodal treatment allocation in soft tissue sarcoma.Histological subtype and grading are cornerstones of treatment decisions in soft tissue sarcoma (STS). Due to intratumoral heterogeneity, pretreatment grading assessment is frequently unreliable and may be improved through functional imaging. In this pilot study, 12 patients with histologically confirmed STS were included. Preoperative functional magnetic resonance imaging was fused with a computed tomography scan of the resected specimen after collecting core needle biopsies and placing radiopaque markers at distinct tumor sites. The Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grading criteria of the biopsies and apparent diffusion coefficients (ADCs) of the biopsy sites were correlated. Concordance in grading between the specimen and at least one biopsy was achieved in 9 of 11 cases (81.8%). In 7 of 12 cases, fusion imaging was feasible without relevant contour deviation. Functional analysis revealed a tendency for high-grade regions (Grade 2/3 (G2/G3)) (median (range) ± standard deviation: 1.13 (0.78–1.70) ± 0.23 × 10−3 mm2/s) to have lower ADC values than low-grade regions (G1; 1.43 (0.64–2.03) ± 0.46 × 10−3 mm2/s). In addition, FNCLCC scoring of multiple tumor biopsies proved intratumoral heterogeneity as expected. The ADC appears to correlate with the FNCLCC grading criteria. Further studies are needed to determine whether functional imaging may supplement histopathological grading.

A better overall survival (OS) for total (ipsilateral) retroperitoneal lipectomy than standard complete resection in patients with retroperitoneal liposarcoma: a comparative multi-institutional study.

BackgroundComplete resection (CR) serves as the standard of surgical treatment for retroperitoneal liposarcoma (RPLS). Unfortunately, even at referral centers, recurrence rates are high, and CR may not address multifocal diseases, which are a common phenomenon in RPLS. We sought to retrospectively compare the clinical outcomes of RPLS patients treated with total (ipsilateral) retroperitoneal lipectomy (TRL) and CR. Because TRL remove potentially multifocal tumors in the fat, patients may have a better prognosis than CR.MethodsPatients with primary/first-recurrent RPLS who had been treated at 5 referral centers were recruited from December 2014 to June 2018. Multivariable Cox regression analyses were conducted to determine the effects of demographic, operative, and clinicopathological variables on the following primary endpoints: local recurrence (LR), local recurrence-free survival (LRFS), and overall survival (OS).ResultsA total of 134 patients were enrolled in this retrospective study, 53 of whom underwent TRL, and 81 of whom underwent CR. The 2 groups were comparable in terms of age, gender, presentation (primary vs. first-recurrent RPLS), number of tumors (unifocal vs. multifocal) at presentation, and Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grade. The TRL group had higher levels of preoperative hemoglobin (Hb) (13 vs. 12.5 g/dL; P=0.008) and a lower amount of intraoperative blood loss (400 vs. 500 mL; P=0.034), but there were no significant differences in the length of hospital stay (23 vs. 22 d; P=0.47) or complications (32 vs. 30; P=0.82) between the 2 groups. In a subset of patients with multifocal tumors at initial presentation, OS was more prolonged in those treated with TRL than those treated with CR (P=0.0272). Based on the multivariable analysis, primary liposarcoma and a low FNCLCC grade were associated with decreased LR and improved OS.ConclusionsTRL is a safe procedure that positively affects the OS of patients with multifocal RPLS. This novel strategy deserves further investigation in prospective studies.

Clinicopathologic and molecular analyses of cutaneous leiomyosarcoma: A retrospective, multicenter study of 79 cases

To the Editor: Cutaneous leiomyosarcoma (cLMS) is a rare skin sarcoma reported to have a good prognosis.1Winchester D.S. Hocker T.L. Brewer J.D. et al.Leiomyosarcoma of the skin: clinical, histopathologic, and prognostic factors that influence outcomes.J Am Acad Dermatol. 2014; 71: 919-925https://doi.org/10.1016/j.jaad.2014.07.020Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar In this large, retrospective, and multicenter study of cLMS (confined to the dermis or involving the subcutis layers), conducted from January 2000 to June 2019, we aimed to better define its clinicopathologic features and prognostic factors. Statistical analyses combined the Kaplan-Meier method (to estimate overall survival and progression-free survival) and the log-rank test (to identify prognostic factors). We also performed molecular analyses using whole-genome copy number analyses as well as targeted DNA and RNA sequencing. Seventy-nine patients were included (Supplementary Table I, available via Mendeley at https://data.mendeley.com/datasets/sjk9p9rgtz/1). Most cases occurred in the lower portion of the limbs (n = 29 [36.7%]) and showed subcutis invasion (n = 35 [44.3%]) and a low histologic grade (grade I, n = 49, [62.0%]) according to the Fédération Nationale des Centres de Lutte Contre le Cancer2Coindre J.M. Trojani M. Contesso G. et al.Reproducibility of a histopathologic grading system for adult soft tissue sarcoma.Cancer. 1986; 58: 306-309https://doi.org/10.1002/1097-0142(19860715)58:2<306::aid-cncr2820580216>3.0.co;2-7Crossref PubMed Google Scholar grading system. The margin status was R0 in 59 cases (74.7%, ie, complete surgical resection, without residual tumor). Recurrence occurred in 12 patients (15.2%), whereas regional or distant metastasis occurred in 7 patients (8.9%). Eight patients died, 6 of them because of metastatic cLMS. The median overall survival and progression-free survival was 38.8 (range, 4.9-73.9) and 25.2 months (range, 2.8-66.1), respectively. The estimated 24-month overall survival and progression-free survival rates were 92% and 77%, respectively. There was no significant association between outcomes and clinical parameters (age, sex, tumor location, and tumor size). However, the margin sizes were wider in the population without relapse (n = 33, margin size = 1.80 cm) than in the population with relapse (n = 9, margins size = 1.06 cm, P = .03). Conversely, an intermediate or high Fédération Nationale des Centres de Lutte Contre le Cancer grade (II-III) was significantly associated with a higher risk of recurrence or metastasis (hazard ratio, 4.8; 95% CI, 1.6-14.6; P = .01). There was no prognostic association with other histologic factors; the hazard ratio of the recurrence/metastasis of subcutis invasion was 7.4 (95% CI, 0.9-58.2; P = .06). Subcutis invasion (n = 35) was observed in 51% of cases with grade I versus 40% of cases with grade II/III cLMS. Eleven cases were molecularly explored, showing heterogeneous profiles (Supplementary Table II, available via Mendeley at https://data.mendeley.com/datasets/8t7hcb8jw7/1): 4 cases presented with >10 segmental copy number alterations (CNAs) (case numbers, 1-4), 3 cases presented with only 1 CNA (case numbers, 5-7). The recurrent abnormalities were the deletion of the RB1 (n = 5) or TP53 gene (n = 4) and the amplification of MYOCD (n = 2). Four cases presented with no CNA (case numbers, 8-11). TP53 mutations were identified, but no fusion gene was identified. The limitation of this study is its retrospective design; nevertheless, the following data deserve to be highlighted. cLMS has a good prognosis, with the 5-year survival rate ranging from 86% (in our series) to 92% (Surveillance, Epidemiology, and End Results Database). However, recurrence/metastasis may have occured.1Winchester D.S. Hocker T.L. Brewer J.D. et al.Leiomyosarcoma of the skin: clinical, histopathologic, and prognostic factors that influence outcomes.J Am Acad Dermatol. 2014; 71: 919-925https://doi.org/10.1016/j.jaad.2014.07.020Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar,3Wong G.N. Webb A. Gyorki D. et al.Cutaneous leiomyosarcoma: dermal and subcutaneous.Australas J Dermatol. 2020; 61: 243-249https://doi.org/10.1111/ajd.13307Crossref PubMed Scopus (5) Google Scholar Few previous studies correlated prognosis with clinicohistologic parameters.3Wong G.N. Webb A. Gyorki D. et al.Cutaneous leiomyosarcoma: dermal and subcutaneous.Australas J Dermatol. 2020; 61: 243-249https://doi.org/10.1111/ajd.13307Crossref PubMed Scopus (5) Google Scholar We reported for the first time that Fédération Nationale des Centres de Lutte Contre le Cancer grading is the most important prognostic factor. Therefore, cLMS of grade II/III should be managed with wider local excision, as already suggested, and we recommend margins of 2 cm.4Kazlouskaya V. Lai Y.C. Khachemoune A. Leiomyosarcoma of the skin: review of the literature with an emphasis on prognosis and management.Int J Dermatol. 2020; 59: 165-172https://doi.org/10.1111/ijd.14705Crossref PubMed Scopus (9) Google Scholar Our study was the first to explore pan-genomic CNAs as well as targeted mutations and fusion genes. Patients with cLMS with a complex genomic quantitative profile (case numbers, 1-4, which showed subcutaneous extension) share some molecular features described in patients with deep soft tissue leiomyosarcoma: TP53 and RB1 alterations and MYOCD amplification.5Dry S.M. Fröhling S. Leiomyosarcoma. WHO Classification of Soft Tissue and Bone Tumours.5th ed. IARC, 2019: 195-197Google Scholar Patients with cLMS with such molecular features might have a pejorative prognosis, which should be confirmed in a larger cohort. None disclosed.

COVID-19 Infections in Cancer Patients Were Frequently Asymptomatic: Description From a French Prospective Multicenter Cohort (PAPESCO-19).

Background:Cancer patients (CPs) are considered more vulnerable and as a high mortality group regarding COVID-19. In this analysis, we aimed to describe asymptomatic COVID (+) CPs and associated factors.Methods:We conducted a prospective study in CPs and health care workers (HCWs) in 4 French cancer centers (PAPESCO [PAtients et PErsonnels de Santé des Centres de Lutte Contre le Cancer pendant l’épidémie de COvid-19] study). This analysis used data recorded between June 17, 2020 and November 30, 2020 in CPs (first 2 waves, no variants). At inclusion and quarterly, CPs reported the presence of predefined COVID-19 symptoms and had a blood rapid diagnostic test; a reverse transcription polymerase chain reaction (RT-PCR) was done in case of suspected infection.Results:A total 878 CPs were included; COVID-19 prevalence was similar in both CPs (8%) and HCWs (9.5%); of the 70 CPs (8%) who were COVID (+), 29 (41.4%) were and remained asymptomatic; 241/808 of the COVID (−) (29.8%) were symptomatic. 18 COVID (+) were hospitalized (2% of CPs), 1 in intensive care unit (ICU) and 1 died (0.1% of CPs and 2.4% of symptomatic COVID [+] CPs). Only the inclusion center was associated with clinical presentation (in Nancy, Angers, Nantes, and Clermont-Ferrand: 65.4%, 35%, 28.6%, and 10% CPs were asymptomatic, respectively).Conclusions:Seroprevalence of COVID-19 in CPs was similar to that observed in HCWs; mortality related to COVID-19 among CPs was 0.1%. More than 40% of COVID (+) CPs were asymptomatic and one third of COVID (−) CPs had symptoms. Only geographic origin was associated with the presence or absence of symptoms. Social distancing and protective measures must be applied in CPs at home and when hospitalized.

Breast Primary Angiosarcoma: A Clinicopathologic and Imaging Study of a Series Cases.

The aim of our study is to provide clinicopathologic and imaging features of breast primary angiosarcoma. We retrospectively analyzed cases of primary angiosarcoma diagnosed at the Pathological Laboratory of Lomé over a period of 20 years (2000-2019). Eight cases of primary angiosarcoma of the breast were collected, including 6 from women and 2 from men. The median age was 41.63 years (range from 17 to 66 years). Depending on the location, there were 4 of 8 cases in the left breast. Ultrasound classifications were BI-RADS 4 and 5. Histology revealed a malignant vascular proliferation composed of small lumens lined by atypical endothelial cells, evident mitoses, and foci of necrosis. On immunohistochemistry, the lesional cells expressed CD31, CD34, and Factor VIII. Based on Federation Nationale des Centers de Lutte Contre Le Cancer (FNCLCC) grading, the cases were grade II and III. Overall survival at 6 months was estimated to be 25% in a woman.

Fédération Nationale Des Centres de Lutte Contre Le Cancer (FNCLCC) Grading, Margin Status and Tumor Location Associate With Survival Outcomes in Malignant Peripheral Nerve Sheath Tumors.

Histologic grading using the Fédération Nationale des Centres de Lutte Contre Le Cancer (FNCLCC) system is not universally accepted as applicable to malignant peripheral nerve sheath tumor (MPNST), as its prognostic value is not well established. We retrospectively evaluated 99 cases of MPNST to investigate any association between the outcomes overall survival (OS) and progression-free survival (PFS), and predictor variables FNCLCC grade, clinical setting, tumor location, and tumor size at diagnosis using multivariable Cox proportional hazard analysis. Univariable and multivariable analysis demonstrate a statistically significant association between FNCLCC grade and both OS and PFS when comparing tumors by histologic grade. Of note, no deaths were observed in patients with grade 1 MPNST. Other variables associated with unfavorable outcomes include fragmented resection and primary site, with tumors in the extremities having favorable OS, but not PFS, when compared with those in truncal locations. Tumors in the head and neck had favorable PFS, but not OS, compared with those in the trunk. No statistically significant differences in OS or PFS were observed when comparing patient age and sex, tumor size at diagnosis, clinical setting (primary vs. type-1 neurofibromatosis vs. radiation associated) or history of neoadjuvant therapy. Interobserver agreement for FNCLCC grading of these tumors was considered good (S*=0.77, 95% confidence interval: 0.71-0.84). Association between FNCLCC grading and survival outcomes in MPNST suggests potential value to routinely grading these neoplasms. However, the subjectivity of the grading system, particularly when assigning a tumor differentiation score, may pose a challenge, especially in low and intermediate grade lesions.

Clinical value of baseline 18F-FDG PET/CT in soft tissue sarcomas

BackgroundThe use of 18F-FDG Positron emission tomography/Computed tomography (PET/CT) in the initial staging of many cancers is clearly established. Most soft tissue sarcoma (STS) has a high affinity for 18F-FDG, which is why 18F-FDG PET/CT has been proposed as a non-invasive method, useful in diagnosis and follow-up. The standardized uptake value values (SUV), the volume-based metabolic parameters MTV (metabolic tumor volume), and TLG (total lesion glycolysis) determine tumor viability and provide its total volume and the total activity of metabolically active tumor cells. The histological grade is the most important predictor of metastases and mortality associated with STS, and a significant relationship between the metabolic parameters of 18F-FDG PET/CT and the histological grade has been described.MethodsA retrospective study was conducted on STS patients, who had histological grade according to the FNCLCC (Fédération Nationale des Centres de Lutte Contre Le Cancer) criteria, as well as a baseline PET/CT. SUV (SUVmax, SUVmean, and SUVpeak), MTV, and TLG were quantified. A T-student test was performed to establish the relationship between the metabolic biomarkers and the histological grade. Their usefulness as predictors of the histological grade was verified using receiver operator characteristic (ROC) curves. A survival function study was performed using the Kaplan–Meier method. To assess the prognostic utility of the metabolic biomarkers we use the Log-Rank method.ResultsThe SUV values were useful to discriminate high-grade STS. We found a significant relationship between the histological grade and the SUV values. SUVmax, SUVpeak, MTV, and TLG were predictors of overall survival (OS). There were no significant differences in the OS for the SUVmean, or in the disease-free survival (DFS) for SUVmax, SUVmean, SUVpeak, MTV, and TLG.ConclusionsThe SUVmax, SUVmean, and SUVpeak values correlate with the HG and are useful to discriminate high-grade from low-grade STS. Patients with high SUVmax, SUVpeak, MTV, and TLG have a significantly lower OS.

Dedifferentiated Liposarcoma: A Comprehensive Historical Review With Proposed Evidence-based Guidelines Regarding a Diagnosis in Need of Further Clarification.

Among all sarcoma types, liposarcoma is the most common sarcoma that develops "dedifferentiation." Since its initial description by Dr Harry Evans, the spectrum of what is now acceptably included under the rubric of "dedifferentiated liposarcoma" (DL) has expanded, sometimes supported by cytogenetic and molecular advances. Similarly, the range of morphologic appearances considered to represent the precursor of DL, atypical lipomatous tumor (ALT)/well-differentiated liposarcoma, also has broadened, not uncommonly creating variants with significant, almost indistinguishable, morphologic overlap with occasional forms of DL, especially problematic in small biopsy specimens. More specifically, the precise criteria separating cellular forms of ALT from what some consider "low-grade" variants of DL remains controversial and inconsistently applied, even among individual pathologists within institutions. For this separation, the only objective and reproducible criteria historically shown to accurately predict a statistically significant difference in prognosis and survival is mitotic rate, alone or incorporated into a histologic grade [eg, Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC)], consistently identifying a higher grade neoplasm capable of metastases. While DL may have a better prognosis than other nonmyoid adult pleomorphic soft tissue sarcomas, definitive conclusions are difficult to establish due to nonuniform criteria for staging and establishing tumor size/volume of the high-grade component, compounded by variable definitions and thresholds for rendering the diagnosis of DL. If appropriate therapeutic approaches are to be applied to DL, there needs to uniform agreement regarding the histologic definition, grading, and staging of DL. Herein, is a comprehensive historical perspective on DL and ALT/well-differentiated liposarcoma, seeking to provide insights, updates, and a proposal for uniform, evidence-based guidelines.

Ki-67 immunoexpression and radiological assessment of necrosis improves accuracy of conventional and modified core biopsy systems in predicting the final grade assigned to adult-soft tissue sarcomas. An international collaborative study

Based on the French Federation Nationale des Centers de Lutte Contre le Cancer (FNCLCC) grading system, this study assesses the accuracy of conventional and modified core biopsy (CB) systems in predicting the final grade (low vs high) assigned to the resected specimen. Substituting Ki-67 immunoexpression for mitotic count, and radiological for histological assessment of necrosis, we used two modified FNCLCC CB grading systems: (1) Ki-67 immunoexpression alone, and (2) Ki-67 plus radiological assessment of necrosis. We graded 199 soft tissue sarcomas (STS) from nine centers, and compared the results for the conventional (obtained from local histopathology reports) and modified CB systems with the final FNCLCC grading of the corresponding resected specimens. Due to insufficient sample quality or lack of available radiologic data, five cases were not evaluated for Ki67 or radiological assessment of necrosis. The conventional FNCLCC CB grading system accurately identified 109 of the 130 high-grade cases (83.8%). The CB grading matched the final FNCLCC grading (low vs high) in 175 (87.9%) of the 199 resected tumors; overestimating the final grade in three cases and underestimating in 21 cases. Modified system 1 (Ki-67) accurately identified 117 of the 130 high-grade cases (90.0%). The CB grading matched the final FNCLCC grading (low vs high) in 175 (89.7%) of the 195 evaluated cases; overestimating seven and underestimating 13 cases. Modified system 2 (Ki-67 plus radiological necrosis) accurately identified 120 of the 130 high-grade cases (92.3%). This last matched the final FNCLCC grading (low vs high) in 177 (91.2%) of the 194 evaluated cases; overestimating seven and underestimating 10 cases. Modified system 2 obtained highest area under ROC curves, although not statistically significant. Underestimated CB grades did not correlate with histological subtypes, although many of the discrepant cases were myxoid tumors (myxofibrosarcomas or myxoid liposarcomas), leiomyosarcomas or undifferentiated pleomorphic/spindle cell sarcomas. Using modified FNCLCC CB grading systems to replace conventional mitotic count and histologic assessment of necrosis may improve the distinction between low and high-grade STS on CB. Our study confirms that classifying grade 1 as low grade and grades 2 and 3 as high grade improves correlation between CB and final grade by up to 21%, irrespective of CB system used. A higher than expected Ki-67 score in a low-grade sarcoma diagnosed on CB should raise concern that a higher-grade component may not have been sampled. Furthermore, correlation of all clinicopathological and radiological findings at multidisciplinary meetings is essential to assess the histological grade on CB as accurately as possible.

Retroperitoneal Dedifferentiated Liposarcoma.

We aimed to test the hypothesis that in retroperitoneal dedifferentiated liposarcoma (DDLS) the presence of the dedifferentiated (DD) component at the resection margin is associated with adverse outcome. We retrospectively searched the archive for primary resections of retroperitoneal DDLS performed at our institution between 1990 and 2017. Slides were rereviewed for diagnosis, Fédération Nationale des Centres de Lutte Contre le Cancer grade, myogenic differentiation, and the presence of the well-differentiated (WD) or DD component at the resection margin. The medical records were reviewed for patient age, sex, tumor size, tumor focality, adjuvant/neoadjuvant therapy, local recurrence, distant metastases, local recurrence-free survival (LRFS), overall survival (OS), and follow-up duration. The presence of the DD component at the resection margin was associated with worse LRFS compared with cases without the DD component at the margin (P = .002). However, OS was not significantly affected (P = .11). LRFS is significantly shorter in cases with the DD component at the margin compared with cases without DD tumor at the margin, while there is no association with OS. We recommend reporting the presence or absence of DD tumor at the margin in retroperitoneal DDLS, as it adds meaningful prognostic information.

Paediatric soft tissue sarcomas in a resource constraint setting: Grade and stage at presentation and at oncologic intervention are usually of poor prognostic characteristics.

To describe the pattern of paediatric Rhabdomyosarcomas (RMS) and Non-Rhabdomyosarcomas (NRMS) with emphasis on the indices that affect survival outcomes. We reviewed all patients with histologically confirmed RMS and NRMS in the Departments of Pathology and Paediatrics, University College Hospital (UCH), Ibadan, Nigeria; in children aged 0-14years. The study period was January 1991 to December 2016. Information obtained included age, gender, morphology and site of the tumours. The tumour grade and pathologic/clinical staging of all patients were also obtained and verified by the clinical records. Tumour grading was carried out using the Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) Sarcoma group grading system and staging was done using TNM. Follow up, survival information and final outcome were retrieved. The 104 patients included in the study had almost equal male-to-female ratio, age ranged between 5months and 14years (median 8.2years). Rhabdomyosarcoma had mean age of 5.6 (±3.8) years while that of NRMS was 9.2(±4.1) years. Overall, the modal age group was 5-9years. Rhabdomyosarcoma was the commonest histological type (76%), undifferentiated sarcomas (6.7%), fibrosarcoma (3.8%) and 2.9% each for synovial sarcoma and dermatofibrosarcoma protuberans. The common primary sites were the head and neck (including the orbit) 49 (47.1%), and the abdominopelvic 26 (25%) regions. Majority (89%) had histologic grade 3 at presentation. Seventy per cent and 64% of patients with RMS and NRMS, respectively, had high stage tumour at presentation. Median survival for all patients with Rhabdomyosarcoma was 45weeks with a 1-year survival of 43% and 2-year survival of 25%. Non-RMS (Dermatofibrosarcoma protuberans and Solitary fibrous tumours) had survival of over 4year's duration. Majority of our patients presented at a late stage with histologic high grade which confers poor prognosis and reduced chances for good overall survival outcome.

Retroperitoneal sarcomas: Outcomes of repeated resections.

Retroperitoneal sarcomas (RPS) are rare malignant tumors arising from mesenchymal cells. The objective of this study was to review the treatment experiences and to identify prognostic factors for overall survival (OS) after primary resection and subsequent reoperations for recurrences. The medical records of patients who underwent resection for RPS at our institution between June 2002 and December 2016 were retrospectively reviewed. Univariate and multivariable Cox proportional hazards modeling was used to assess the prognostic factors for OS. A total of 48 patients were enrolled. On multivariable analysis in primary resection group, the FNCLCC (Fédération Nationale des Centres de Lutte Contre le Cancer) grade was a significant prognostic factor for OS (P=0.006). The patients who received chemotherapy after primary resection were significantly associated with poor prognosis (P=0.009). The 5-year OS rate after primary resection (n=48) were 58.1% and the 5-year cumulative reoperation rate after primary resection was 62.5%. After second resection for recurrence after primary resection (n=23), the 5-year OS rate was 64.3%. There was a tendency towards decreased surgery-free survival rate as the number of repeated resections for recurrent RPS increased. In the subset of patients (n=16) who underwent more than 3 repeated resections at our institute, the 5-year OS rate was 75.0%, indicating that repeated resections are not associated with worse outcome. Only low tumor grade was an independent favorable prognostic factor for OS. Although the prognosis for RPS remains poor, repeated resections for recurrence are not associated with poor prognosis. Aggressive surgical strategies for recurred RPS patients are warranted.

RADT-20. HISTOPATHOLOGIC FINDINGS IN MALIGNANT PERIPHERAL NERVE SHEATH TUMOR ARE BOTH PROGNOSTIC FOR OVERALL SURVIVAL AND PREDICTIVE FOR RESPONSE TO RADIATION THERAPY

Abstract BACKGROUND Malignant peripheral nerve sheath tumor (MPNST) is an aggressive neoplasm associated with neurofibromatosis type 1 (NF1). Despite multimodal therapy, clinical outcomes remain poor. To elucidate markers of MPNST treatment response, we retrospectively reviewed the medical records of MPNST patients at a single institution and performed histopathological and immunohistochemical (IHC) analysis for predictive and prognostic features. METHODS We identified 54 consecutive patients treated at University of California San Francisco between 1990 and 2018 that met diagnostic criteria for MPNST on pathologic review with sufficient tissue available for histology and immunohistochemistry (IHC) assays. IHC was performed for Ki-67, EGFR, p53, H3K27me3, neurofibromin, S100, p75NTR, SOX10, p16, and SOX2. Overall survival (OS), metastasis free survival (MFS), and locoregional failure free rate (LFFR), were estimated using the Kaplan-Meier method. Log-rank test, Cox Proportional Hazards regression, and hierarchical clustering were performed in R. RESULTS With a median follow up of 19.2 months, the 5-year OS, MFS, and LFFR were 58%, 68%, and 66%, respectively, with no significant differences between NF1 associated (n=32) and sporadic tumors (n=22). Radiation therapy significantly improved 5-year LFFR (80% versus 49%, p=0.05), but not OS or MFS. Tumor grade was associated with worse OS by Fédération Nationale des Centres de Lutte Contre Le Cancer (FNCLCC) grading (p=0.02). Furthermore, elevated Ki-67 index was associated with worse 5-year OS (39% versus 73% for Ki-67 index ³ 60 and Ki-67 index &amp;lt; 60, p=0.01). Finally, hierarchical clustering of IHC data identified a predictive signature defined by elevated Ki-67 and EGFR expression associated with improved responses to radiation therapy (5-year OS 86% versus 10%, p=0.004). CONCLUSIONS Our data provide insights into the diagnosis and treatment of MPNST. Additional investigation is needed to understand the biologic mechanisms and generalizability of the signatures uncovered in our analysis.

The Effect of Resection Margin on Local Recurrence and Survival in High Grade Soft Tissue Sarcoma of the Extremities: How Far Is Far Enough?

Simple SummaryIn soft tissue sarcomas the width of surgical margins after resection determines the extent of surgery and the function after resection. But how far is really necessary? 305 patients with deep-seated, G2/3 soft tissue sarcomas of the extremity, the trunk wall, or the pelvis were reviewed. The 5-year local recurrence-free survival (LRFS) was 82%. Overall survival (OS) at 5 years was 66%. Positive (contaminated) margins worsened LRFS and OS. A margin of >10 mm did not improve LRFS and OS as compared to one of >5 mm. A resection margin of <1 mm showed a trend but not significantly better LRFS or OS compared to a contaminated margin. In conclusion the margin should at least be free of tumor, in sound tissue. A margin of >5 mm sound tissue seems to be sufficient. Resecting more tissue does not benefit the patient.Background: The significance of surgical margins after resection of soft tissue sarcomas in respect to local-recurrence-free survival and overall survival is evaluated. Methods: A total of 305 patients with deep-seated, G2/3 soft tissue sarcomas (STS) of the extremity, the trunk wall, or the pelvis were reviewed. The margin was defined according to the Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) classification system (R0-2), the Union Internationale Contre le Cancer (UICC) classification (R + 1 mm) for which a margin <1 mm is included into the R1 group, and in groups of <1 mm, 1–5 mm, >5 mm, or >10 mm. Results: Of these patients, 31 (10.2%) had a contaminated margin, 64 (21%) a margin of <1 mm, 123 (40.3%) a margin of 1–5 mm, 47 (15.4%) a margin of >5 mm, and 40 (13.1%) a margin of >10 mm. The 5-year local recurrence-free survival (LRFS) was 81.6%. Overall survival (OS) at 5 years was 65.9%. Positive margins worsened LRFS and OS. A margin of >10 mm did not improve LRFS and OS as compared to one of >5 mm. Conclusions: A resection margin of <1 mm showed a trend but not significantly better LRFS or OS compared to a contaminated margin. This finding supports use of the UICC classification. A margin of more than 10 mm did not improve LRFS or OS.

A case of retroperitoneal dedifferentiated liposarcoma successfully treated by neoadjuvant chemotherapy and subsequent surgery

BackgroundRetroperitoneal liposarcoma (RPLS) is the most commonly observed soft tissue sarcoma in the retroperitoneal space. Although the beneficial effect of chemotherapy for RPLS is controversial, there are some reports that have shown a considerable tumor-suppressive effect of chemotherapy in RPLS. We demonstrate a case of dedifferentiated RPLS, which was initially considered inoperable but was successfully treated by neoadjuvant chemotherapy and subsequent curative resection.Case presentationA 59-year-old female was referred to our hospital with a chief complaint of right lower quadrant abdominal pain. Abdominal computed tomography revealed a large retroperitoneal tumor with a maximum diameter of 11 cm. The tumor involved retroperitoneal major vasculatures, such as the right common iliac vein and artery, as well as the right psoas muscle and femoral nerve. The right ureter was also involved and obstructed by the tumor. A biopsy was performed through the retroperitoneal route, and the tumor was diagnosed as a dedifferentiated liposarcoma with the Fédération Nationale des Centres de Lutte Contre le Cancer grade 3. Because the tumor was highly invasive and complete resection was not feasible, we decided to administer neoadjuvant chemotherapy with doxorubicin and ifosfamide (AI). After completing 6 courses of AI, the tumor size was considerably reduced, and we decided to perform surgery with curative intent. Before laparotomy, femoro-femoral arterial bypass was performed to prepare for the right common iliac artery resection. Thereafter, the patient underwent laparotomy and tumor resection combined with right nephrectomy, resection of the right common iliac artery and vein, and resection of the right psoas muscle and femoral nerve. The postoperative course was uneventful, although the patient needed a walking brace to support her gait. The pathological findings indicated a 99% disappearance of tumor cells. The patient was healthy without any complaints after 1 year of surgery, and a follow-up CT scan revealed no tumor recurrence.ConclusionsTo the best of our knowledge, this is the first report that showed a nearly complete pathological response to AI in dedifferentiated RPLS, which was subsequently completely resected.

MR T1WI based radiomics and machine learning model for predicting the histopathological grades of soft tissue sarcomas

Objective To explore the value of T1WI based optimal radiomics and machine learning model in predicting histological grades of soft tissue sarcoma. Methods The preoperative MR T1WI data of 113 patients with soft tissue sarcoma in Affiliated Hospital of Qingdao University from May 2009 to November 2018 was analyzed retrospectively. The patients were divided into training set (n=80) and validation set (n=33) using randomly stratified sampling mothed. According to the French Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC) system, the soft tissue sarcomas were divided into 3 pathological levels (grade Ⅰ-Ⅲ). Grade Ⅰ was defined as low grade, grade Ⅱ and Ⅲ were defined as high grade. In the training set, there were 18 cases with low-grade lesions, 62 cases with high-grade lesions. In the validation set, there were 7 cases with low-grade lesions and 26 cases with high-grade lesions. After a normalizationapproach applied on the image, the radiomics features were extracted in the regions of interest using A.K software. Based on different feature selection methods [with or without recursive feature elimination (RFE)], machine learning algorithm [random forest (RF) or support vector machine (SVM)] and sampling technology [without subsampling, with the synthetic minority oversampling technique (SMOTE) or with random oversampling examples], a total of 12 models were built and each machine-learning combination model was trained using leave-one-out cross validation. The receiver operating characteristic (ROC) curves were used to evaluate the efficacy of the model in predicting the pathological grade of soft tissue sarcoma. Results Among the 12 different machine learning models, the optimal classification model for the prediction of soft tissue sarcoma pathological grade was a combination of RF, RFE and SMOTE, with an area under the curve of 0.909 (95% confidence interval, 0.808-1.000) in the validation set, and the accuracy, sensitivity, and specificity were 84.85%, 86.21%, and 75.00%, respectively. Conclusion The radiomics based machine learning model can be used as an attractive application approach for predicting histological grades of soft tissue sarcoma. Key words: Magnetic resonance imaging; Soft tissue neoplasms; Sarcoma; Radiomics; Artificial intelligence

Histopathologic findings in malignant peripheral nerve sheath tumor predict response to radiotherapy and overall survival.

Malignant peripheral nerve sheath tumor (MPNST) is an aggressive and poorly understood malignant neoplasm. Even in the setting of multimodal therapy, the clinical course of MPNST is frequently marked by metastatic conversion and poor overall prognosis, with optimal treatment paradigms for this rare tumor unknown. We reviewed the medical records and histopathology of 54 consecutive patients who were treated at University of California San Francisco between 1990 and 2018. Our cohort consisted of 24 male and 30 female patients (median age 38 years). Fédération Nationale des Centres de Lutte Contre Le Cancer (FNCLCC) sarcoma grading criteria segregated patients into groups with differences in overall survival (OS) (P = .02). Increasing Ki-67 labeling index was associated with poor OS (hazard ratio [HR] 1.36 per 10%, P = .0002). Unsupervised hierarchical clustering-based immunohistochemical staining patterns identified 2 subgroups of tumors with differences in H3K27me3, Neurofibromin, S100, SOX10, p16, and EGFR immunoreactivity. In our cohort, cluster status was associated with improved locoregional failure-free rate (P = .004) in response to radiation. Our results lend support to the FNCLCC sarcoma grading criteria as a prognostic scheme for MPNST, although few cases of grade 1 were included. Further, we identify increased Ki-67 labeling as a strong predictor of poor OS from MPNST. Finally, we identify a subset of MPNSTs with a predictive immunohistochemical profile that has improved local control with adjuvant radiotherapy. These data provide insights into the grading and therapy for patients with MPNST, although further studies are needed for independent validation.

Development and external validation of a dynamic prognostic nomogram for primary extremity soft tissue sarcoma survivors

BackgroundPrognostic nomograms for patients with extremity soft tissue sarcoma (eSTS) typically predict survival or the occurrence of local recurrence or distant metastasis at time of surgery. Our aim was to develop and externally validate a dynamic prognostic nomogram for overall survival in eSTS survivors for use during follow-up. MethodsAll primary eSTS patients operated with curative intent between 1994 and 2013 at three European and one Canadian sarcoma centers formed the development cohort. Patients with Fédération Française des Centres de Lutte Contre le Cancer (FNCLCC) grade II and grade III eSTS operated between 2000 and 2016 at seven other European reference centers formed the external validation cohort. We used a landmark analysis approach and a multivariable Cox model to create a dynamic nomogram; the prediction window was fixed at five years. A backward procedure based on the Akaike Information Criterion was adopted for variable selection. We tested the nomogram performance in terms of calibration and discrimination. FindingsThe development and validation cohorts included 3740 and 893 patients, respectively. The variables selected applying the backward procedure were patient's age, tumor size and its interaction with landmark time, tumor FNCLCC grade and its interaction with landmark time, histology, and both local recurrence and distant metastasis (as first event) indicator variables. The nomogram showed good calibration and discrimination. Harrell C indexes at different landmark times were between 0.776 (0.761–0.790) and 0.845 (0.823–0.862) in the development series and between 0.675 (0.643–0.704) and 0.810 (0.775–0.844) in the validation series. InterpretationA new dynamic nomogram is available to predict 5-year overall survival at different times during the first three years of follow-up in patients operated for primary eSTS. This nomogram allows physicians to update the individual survival prediction during follow-up on the basis of baseline variables, time elapsed from surgery and first-event history.

MRI-Based Radiomic Models Predict Tumor Grading in Soft-Tissue Sarcoma Patients

The treatment decision for soft tissue sarcomas (STS) patients vastly depends on the tumor grading determined by invasive biopsies. In this work, we used quantitative imaging features ("radiomics") of pre-therapeutic magnetic resonance imaging (MRI) scans to develop a non-invasive grading model for the differentiation of low-grade from high-grade STS. MRI scans (T1-weight with fat saturation and contrast enhancement (T1FSGd) and T2-weight with fat saturation (T2FS) sequences), clinical information and French Fédération Nationale des Centres de Lutte Contre le Cancer tumor grading were determined from two retrospective cohorts obtained from two independent institutions (122 and 103 patients). After manual segmentation, preprocessing steps including isotropic resampling, intensity discretization, and N4ITK bias field correction were applied. 1394 radiomic features including volume, intensity, texture, wavelet and local binary pattern were extracted using a software program package in python. Features unstable to segmentation variances by three independent experts with an intra-class coefficient below 0.8 were excluded. The ComBatHarmonization was used to compensate for MRI scanner types. Feature reduction and model generation was performed using the least absolute shrinkage and selection operator (LASSO) algorithm. Performance stability was determined by 1000 fold bootstrapping. All statistical methods were performed in R. Low-grade and high-grade STS were found in 48 (39%) and 74 (61%) patients in the training set, and in 20 (19%) and 83 (81%) patients in the validation set, respectively. T1FSGd and T2FS showed similar performances with area under the curve (AUC) values of 0.94 and 0.90 on the training set (see Table 1 for 95% confidence intervals). On the external validation set, the T2FS-based model showed a better reproducibility with an AUC of 0.76 compared to the T1FSGd model (AUC: 0.68). A clinical model (TNM-stages and age) and a tumor volume model did not predict better than random. Neither a combined radiomic model nor a combination with clinical features improved the predictive capacity. In contrast to T2FS (p=0.811), the T1FSGd radiomic models allowed for significant patient stratification for overall survival in the validation set (p=0.048). Decision curve analysis revealed a similar net benefit as tumor grading for the T1FSGd radiomic model. We first describe MRI-based radiomic models for non-invasive tumor grading of STS. Future studies should aim to further improve the reproducibility of MRI-based studies.Abstract 2323; Table 1Performances for differentiation of low-grade and high-grade STS.Training AUC (95%CI)Independent Validation AUC (95%CI)Radiomics-T1FSGd0.94 (0.892-0.976)0.68 (0.555-0.798)Radiomics-T2FS0.90 (0.829-0.949)0.76 (0.636-0.863)Clinical0.56 (0.455-0.663)0.55 (0.414-0.686)Volume0.56 (0.446-0.668)0.62 (0.464-0.759) Open table in a new tab

Distinguishing soft tissue sarcomas of different histologic grades based on quantitative MR assessment of intratumoral heterogeneity

PurposeTo explore the role of intratumoral heterogeneity on MRI assessed by histogram analysis in differentiating soft-tissue sarcomas (STS) of different grades. Materials and MethodsPatients with primary STS undergoing MRI prior to iatrogenic procedures were included retrospectively. The histologic grade was assigned according to Federation Nationale des Centres de Lutte Contre le Cancer grading system. T1WI and T2WI were normalized by dividing mean signal intensity (SI) of contralateral/near unaffected muscles. Contrast-enhanced T1WI was normalized by computing enhancement ratio (ER) map as (SIpost-SIpre)/SIpre×100, where SIpre and SIpost represent SI of each pixel before and after enhancement. A region of interest (ROI) was manually drawn to include entire tumor area on axial slice with largest tumor diameter. Mean, mode, standard deviation, kurtosis and skewness on ROIs were extracted with ImageJ software. ANOVA/Kruskal-Wallis test was used to determine the significance of differences. ROC curve was applied for statistically significant parameters. P value ≤0.05 was considered statistically significant. ResultsAmong involved 67 patients, 8 were assigned to grade 1, 38 to grade 2 and 21 to grade 3. Skewness (P = 0.022) and kurtosis (P = 0.035) on ER maps were significantly different among STS of different grades. The optimal cutoffs of skewness and kurtosis on ER maps were -0.488 (AUC[95% CI] 0.747[0.557–0.937]; sensitivity/specificity, 62.5%/86.4%) and 0.762 (AUC[95% CI] 0.684[0.548–0.821]; sensitivity/specificity, 76.2%/56.5%), respectively. ConclusionIntratumoral heterogeneity on MRI quantitatively displayed by histogram parameters can differentiate STS of different grades. Skewness and kurtosis on ER maps show the capacity.