Fédération Nationale Des Centres De Lutte Contre Le Cancer Research Articles

Analysis of clinical features, treatment methods, and prognostic influence factors in patients with malignant peripheral nerve sheath tumor

To investigate the clinical features, treatment methods, and prognostic influence factors of patients with malignant peripheral nerve sheath tumor (MPNST). A retrospective analysis was conducted on 96 MPNST patients treated between January 1, 2015 and December 31, 2021. There were 46 males and 50 females, aged between 15 and 87 years (mean, 48.2 years). The tumors were located in the trunk in 50 cases, extremities in 39 cases, and head and neck in 7 cases. The maximum tumor diameter was <5 cm in 49 cases, ≥5 cm in 32 cases, with 15 cases missing data. Tumor depth was deep in 77 cases and superficial in 19 cases. The Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) histological grading was G1 in 9 cases, G2 in 12 cases, and G3 in 34 cases, with 41 cases missing data. There were 37 recurrent MPNST cases, 32 cases with neurofibromatosis type 1 (NF1), and 26 cases in stage Ⅳ. Postoperative adjuvant radiotherapy was administered to 25 patients, perioperative chemotherapy to 45 patients, and anlotinib-targeted therapy to 30 patients. R 0 resection was achieved in 73 cases. Patients were divided into groups based on the presence or absence of NF1, and baseline data between the two groups were compared. Kaplan-Meier curves were generated to assess disease-free survival (DFS) and overall survival (OS) based on various factors (age, gender, presence of NF1, recurrent MPNST, stage Ⅳ MPNST, FNCLCC grade, R 0 resection, tumor location, tumor size, tumor depth, perioperative chemotherapy, postoperative adjuvant radiotherapy, and anlotinib-targeted therapy), and differences between survival curves were analyzed using the Log-Rank test. Multivariate COX proportional hazards regression was used to identify independent prognostic factors for MPNST. Patients with NF1 had a significantly higher proportion of superficial tumors and lower FNCLCC grade compared to those without NF1 ( P<0.05); no significant difference was found for other variables ( P<0.05). Kaplan-Meier analysis showed that recurrent MPNST, stage Ⅳ MPNST, FNCLCC grade, R 0 resection, perioperative chemotherapy, and anlotinib-targeted therapy were factors influencing 1-year DFS ( P<0.05), while stage Ⅳ MPNST, FNCLCC grade, and perioperative chemotherapy were factors affecting 3-year OS ( P<0.05). Multivariate COX proportional hazards regression analysis revealed that recurrent MPNST and high-grade FNCLCC (G3) were independent prognostic factors for 1-year DFS ( P<0.05), while stage Ⅳ MPNST, superficial tumor depth, age over 60 years, postoperative adjuvant radiotherapy, and anlotinib-targeted therapy were independent prognostic factors for 3-year OS ( P<0.05). MPNST patients with NF1 tend to have more superficial tumors and lower FNCLCC grades. FNCLCC grade, R 0 resection, and adjuvant therapies, including radiotherapy and anlotinib-targeted therapy, are closely associated with MPNST prognosis. Complete surgical resection should be prioritized in clinical management, along with adjuvant treatments such as radiotherapy and targeted therapy of anlotinib to improve patient outcomes.

Use of Mitotic Activity and the Size of Any Dedifferentiated Component for Risk Assessment in MDM2-Amplified Liposarcoma.

The characteristic molecular signature for both atypical lipomatous tumor/well-differentiated liposarcoma and dedifferentiated liposarcoma is amplified sequences derived from chromosome 12q13-15, including MDM2 proto-oncogene (MDM2). As the progression of atypical lipomatous tumor/well-differentiated liposarcoma to the more aggressive dedifferentiated liposarcoma has the potential to adversely affect patient outcomes, the extent of the latter component might be important to evaluate. To investigate the correlation between clinicopathologic characteristics, including tumor size, modified Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grade, molecular data, and outcomes in 123 surgically resected MDM2-amplified liposarcomas. Pathology reports and clinical records were reviewed. A log-rank test was used to compare the survival trends, and univariate logistic regression was performed to identify variables associated with adverse events (distant metastasis and/or death), from which the P value was derived to construct a multivariate regression model. In univariate analysis, the largest single dimension of the dedifferentiated component, the percentage of cells with gain of chromosome 12, mitotic count, and the presence of modified FNCLLC grade 3 were associated with adverse events. In multivariate analysis, the largest single dimension of the dedifferentiated component (odds ratio: 1.169; 95% CI: 1.053, 1.299; P = .003), and a higher mitotic count (odds ratio: 1.133; 95% CI: 1.037, 1.237; P = .006) were correlated with adverse events. There was no statistically significant association between current local recurrence status, overall largest tumor dimension, overall tumor volume, MDM2 copy number, or MDM2 to chromosome 12 centromere probe ratio and adverse outcomes. Staging dedifferentiated liposarcoma based on the size of the dedifferentiated component better predicts the outcome.

Impact of resection margin on outcome in soft-tissue sarcomas of the extremities treated with limb-sparing surgery and postoperative radiotherapy

BackgroundThe standard curative treatments for extremity soft tissue sarcoma (ESTS) include surgical resection with negative margins and perioperative radiotherapy. However, the optimal resection margin remains controversial. This study aimed to evaluate the outcomes in ESTS between microscopically positive margin (R1) and microscopically negative margin (R0) according to the Union for International Cancer Control (UICC) (R + 1 mm) classification.MethodsMedical records of patients with localized ESTS who underwent primary limb-sparing surgery and postoperative radiotherapy between 2004 and 2015 were retrospectively reviewed. Patients were followed for at least 5 years or till local or distant recurrence was diagnosed during follow-up. Outcomes were local and distal recurrences and survival.ResultsA total of 52 patients were included in this study, in which 17 underwent R0 resection and 35 underwent R1 resection. No significant differences were observed in rates of local recurrence (11.4% vs. 35.3%, p = 0.062) or distant recurrence (40.0% vs. 41.18%, p = 0.935) between R0 and R1 groups. Multivariate analysis showed that distant recurrences was associated with a Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grade (Grade III vs. I, adjusted hazard ratio (aHR): 12.53, 95% confidence interval (CI): 2.67–58.88, p = 0.001) and tumor location (lower vs. upper extremity, aHR: 0.23, 95% CI: 0.07–0.7, p = 0.01). Kaplan–Meier plots showed no significant differences in local (p = 0.444) or distant recurrent-free survival (p = 0.161) between R0 and R1 groups.ConclusionsR1 margins, when complemented by radiotherapy, did not significantly alter outcomes of ESTS as R0 margins. Further studies with more histopathological types and larger cohorts are necessary to highlight the path forward.

Prognostic evaluation of the Ki-67 labeling system in histological grading of non-small round cell sarcoma: a supplementary analysis of a randomized controlled trial, JCOG1306.

Soft tissue sarcoma (STS) has various histological types and is rare, making it difficult to evaluate the malignancy of each histological type. Thus, comprehensive histological grading is most important in the pathological examination of STS. The Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grading system is most commonly used in daily pathological analysis of STS. Among the FNCLCC grading system parameters, mitotic count is a key morphological parameter reflecting the proliferative activity of tumor cells, although its reproducibility may be lacking. Here, we compared the prognostic utility of the conventional and modified FNCLCC grading systems in JCOG1306. We analyzed 140 patients with non-small round cell sarcoma. We performed Ki-67 immunostaining using open biopsy specimens before preoperative chemotherapy in all patients. We assessed histological grade in individual cases by conventional FNCLCC grading (tumor differentiation, mitotic count, and necrosis) and modified FNCLCC grading using the Ki-67 labeling index instead of mitotic count. We conducted univariable and multivariable Cox regression analyses to investigate the influence of grade on overall survival. In univariable analysis, prognosis was worse for patients with conventional FNCLCC Grade 3 tumors compared with Grade 1 or 2 tumors (hazard ratio [HR] 4.21, 95% confidence interval [CI] 1.47-12.05, P=0.008). Moreover, prognosis was worse in patients with modified FNCLCC Grade 3 tumors compared with Grade 1 or 2 tumors (HR 4.90, 95% CI 1.64-14.65, P=0.004). In multivariable analysis including both conventional and modified FNCLCC grading, the modified grading more strongly affected overall survival (HR 6.70, 95% CI 1.58-28.40, P=0.010). The modified FNCLCC grading system was superior to the conventional system in predicting the prognosis of patients with non-small round cell sarcoma according to this supplementary analysis of data from the randomized controlled trial JCOG1306.

Overexpression of ASPH protein predicts poor outcomes in retroperitoneal liposarcoma patients.

Overexpression of ASPH protein predicts poor outcomes in retroperitoneal liposarcoma patients.

Expression of fibroblast growth factor receptor substrate 2 (FRS2) in primary retroperitoneal liposarcoma and its clinical implications.

The aim of this study was to investigate the expression level of fibroblast growth factor receptor substrate 2 (FRS2) in tissues of patients with primary retroperitoneal liposarcoma (PRPLS) and its correlation with recurrence and prognosis. The pathological specimens, medical records, and follow-up information of patients with PRPLS who underwent radical surgery for the first time in our hospital from January 2013 to December 2016 were retrospectively analyzed. FRS2 protein expression in tissues was determined by immunohistochemistry staining, and the FRS2 protein positive rates in patients with different clinicopathological features were compared. Factors influencing patients' recurrence and survival were determined using the multivariate Cox stepwise regression model. This research enrolled 87 patients with PRPLS, with the number of cases presenting FRS2 protein positive rate and positive rate in pathological tissues accounting for 62.07% (54/87) and 37.93% (33/87), respectively. The positive expression of FRS2 protein varied markedly among patients with different pathological types, FNCC, LCC grade, number of tumors, positive margin, and recurrence and metastasis (with vs. without) (all p<0.05). The 87 patients were followed up for 3.5-102 months (median, 27.5 months), with a postoperative 5-year overall disease-free survival (DFS) rate of 17.24% [median progression-free survival (PFS): 24.7 months] and a 5-year overall survival (OS) rate of 44.83% (median OS: 47.3 months). Kaplan-Meier survival curves revealed significantly shorter PFS and OS in patients with positive FRS2 protein expression vs. those with negative FRS2 protein expression (χ2=6.396, 5.032, p<0.05). According to the univariate analysis, the 5-year overall DFS rate varied significantly among patients with different pathological types, Fédération Nationale des Centres De Lutte Contre le Cancer (FNCLCC) grades, number of tumors, positive margin, and FRS2 protein expression (all p<0.05). Pathological type, FNCLCC grading, tumor number, recurrence and metastasis, positive margin, and FRS2 protein expression were significantly correlated with the 5-year OS rate of patients (all p<0.05). Furthermore, pathological type, FNCLCC grading, multiple tumors, positive margin, and FRS2 protein expression were identified by multivariate Cox regression analysis to be independent factors that affected patients' 5-year DFS and OS rates (all p<0.05), and that relapsed and metastasized patients had a 4.586-fold risk of death than those without recurrence and metastasis. FRS2 shows a high positive rate in the tissues of PRPLS patients and is significantly related to the prognostic recurrence and survival of patients, with potential value in judging the prognosis of patients.

Short term outcome of treatment with percutaneous cross Kirschner wires in paediatric distal humeral metaphyseal diaphyseal junction fractures

Background: Soft tissue sarcomas (STS) are malignant tumours arising from mesenchymal tissue, comprising &lt;1% of all the tumours of the human body and represent the second most common type of solid tumours in children and adolescents. Surgical resection is considered the mainstay of treatment, supported by multimodal therapies including chemotherapy and radiotherapy. Resource-limited countries, like Pakistan, face additional challenges due to inadequate resources. This study presents the experience of management of soft tissue sarcomas presenting to a tertiary care hospital in Central Lahore.&#x0D; Patients and Methods: This was an observational study conducted in Surgical Unit I of Sir Ganga Ram Hospital Lahore from January 2017 till June 2022. American Joint Committee on Cancer (AJCC) staging system and Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) resection classification was applied. Surgical treatment including R0, R1 and R2 resections were carried out. SPSS 23 version was used for statistical analysis of collected data.&#x0D; Results: A total of 36 patients; 24 male (66.7%) and 12 females (33.3%) were included. Anatomical site involvement was observed as 23 (63.8%) limb sarcomas and 13 (36.1%) trunk sarcomas. Out of 36 patients, 20 (55.6%) patients were staged as stage II, 11 (30.5%) patients as stage III and 5 (13.9%) as stage I. Total 17 (47.2%) patients underwent wide excision, 13 (36.1%) patients underwent limited excision, 4 (11.1%) patients underwent compartmental excision and 2 (5.6%) patients underwent palliative excision. &#x0D; Conclusion: Thigh was the commonest site of involvement in extremity sarcomas. Retroperitoneal sarcomas were most frequent among trunk tumours. Leiomyosarcoma was the most common histopathological diagnosis followed by malignant peripheral nerve sheath tumours. Most of the patients presented with stage II disease.&#x0D; Keywords: Soft Tissue Sarcoma, Presentation, Resection, Histology, Outcome

Spectrum of soft tissue sarcomas: Experience of surgery at a tertiary care referral hospital in Central Lahore

Background: Soft tissue sarcomas (STS) are malignant tumours arising from mesenchymal tissue, comprising &lt;1% of all the tumours of the human body and represent the second most common type of solid tumours in children and adolescents. Surgical resection is considered the mainstay of treatment, supported by multimodal therapies including chemotherapy and radiotherapy. Resource-limited countries, like Pakistan, face additional challenges due to inadequate resources. This study presents the experience of management of soft tissue sarcomas presenting to a tertiary care hospital in Central Lahore.&#x0D; Patients and methods: This was an observational study conducted in Surgical Unit I of Sir Ganga Ram Hospital Lahore from January 2017 till June 2022. American Joint Committee on Cancer (AJCC) staging system and Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) resection classification was applied. Surgical treatment including R0, R1 and R2 resections were carried out. SPSS 23 version was used for statistical analysis of collected data.&#x0D; Results: A total of 36 patients; 24 male (66.7%) and 12 females (33.3%) were included. Anatomical site involvement was observed as 23 (63.8%) limb sarcomas and 13 (36.1%) trunk sarcomas. Out of 36 patients, 20 (55.6%) patients were staged as stage II, 11 (30.5%) patients as stage III and 5 (13.9%) as stage I. Total 17 (47.2%) patients underwent wide excision, 13 (36.1%) patients underwent limited excision, 4 (11.1%) patients underwent compartmental excision and 2 (5.6%) patients underwent palliative excision. Recurrence was observed in 8 patients for which palliative 2 (5.6%), limited 3 (8.3%) or potentially curative resection 3 (8.3%) was performed.&#x0D; Conclusion: Thigh was the commonest site of involvement in extremity sarcomas. Retroperitoneal sarcomas were most frequent among trunk tumours. Leiomyosarcoma was the most common histopathological diagnosis followed by malignant peripheral nerve sheath tumours. Most of the patients presented with stage II disease. Resectional surgery, whether curative or palliative, was found to be the management modality of choice. Rhabdomyosarcoma most frequently recurred within 6 months of potentially curative surgery (R1), most likely due to compromised initial resection.

Association of inflammatory complications following resection and immediate reconstruction with soft tissue sarcoma recurrence

Purpose: Wide excision and subsequent reconstruction of the defect are crucial pillars in the treatment of soft tissue sarcoma (STS); however, those procedures carry a relatively high risk of postoperative complications, which could raise oncologic concerns. The present study evaluated the association of postoperative complications after resection and immediate reconstruction with STS recurrence. Methods: We reviewed patients with primary STS who underwent wide resection and immediate reconstruction between 2011 and 2019. Patients were categorized into three groups based on their postoperative inflammatory complication status: no complications, noninflammatory complications, and inflammatory complications. Inflammatory complications were defined as those involving a sustained elevation of inflammatory markers in laboratory tests after postoperative 2 weeks. The cumulative incidence of oncologic events and their respective hazard ratios (HRs) were evaluated using multivariable Cox regression analyses. Results: In total, 94 patients with a median follow-up of 54.8 months were analyzed, including 17 with inflammatory complications, 17 with noninflammatory complications, and 60 with no complications. The three groups showed similar baseline characteristics except for older age and a lower rate of FNCLCC (Fédération Nationale des Centres de Lutte Contre Le Cancer) grade 3 in the inflammatory complications group. The inflammatory complications group showed significantly worse disease-free survival than the no complications group. This difference remained significant after adjustment for other variables in multivariate analyses (HR, 3.485; p=0.019). The development of noninflammatory complications was not associated with oncologic outcomes. Conclusion: Our findings suggest that the development of inflammatory complications following wide excision and immediate reconstruction may be associated with the recurrence of STS.

Concordance of histopathological and radiological grading in soft tissue sarcomas

Aim: The grade of the tumor is essential for planning the treatment strategy in soft-tissue sarcomas (STS). The goal of this study is to determine magnetic resonance imaging features related to histopathological grade and aggressiveness of STS.&#x0D; Material and Method: This retrospective single-center study involved preoperative contrast-enhanced MRI examinations of 64 patients with STS. MRI findings evaluated were; heterogeneity, necrosis, hemorrhage, and relationship with surrounding tissue in T1-weighted (T1W), T2-weighted (T2W), and T1W post-contrast sequences of the lesion. Histological grade was determined with the Fédération Nationale des Centres de Lutte Contre Le Cancer (FNCLCC) grading system, and the aggressiveness of the lesion was measured with the Ki-67 index. &#x0D; Results: Sixty-four patients (mean age 45.5±21.6, M/F ratio 34/30) with STS were included. 33 (51.6%) patients graded as FNCLCC grade 3. On MRI examinations, the absence of necrosis was significantly associated with FNCLCC grade 1 and a low Ki-67 index (p

Soft Tissue Sarcomas of the Head and Neck Region with Skull Base/Intracranial Invasion: Review of Surgical Outcomes and Multimodal Treatment Strategies: A Retrospective Case Series.

Soft tissue sarcomas (STS) invading the skull base are rare with little data to guide surgical management. Here we aimed to determine the factors affecting tumor control rates and survival in patients with T4 stage head and neck STS involving the skull base. A retrospective review of STS patients, surgically treated at our institution between 1994 and 2017 was conducted. Variables were collected and assessed against progression-free survival. Tumors were graded using the Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) system. A total of 51 patients (mean age of 35) were included, of whom 17 (33.3%) patients were FNCLCC grade 1, 8 (15. 7%) were FNCLCC grade 2 and 26 (51%) were FNCLCC grade 3. The median PFS was 236.4 months while the 5- and 10-year PFS rates were 44% and 17%, respectively. Recurrence occurred in 17 (33.3%) patients. Local recurrence occurred in 10 (58.8%). Univariate analysis revealed R0 resection had a near-significant impact on tumor control in radiation-naïve patients. Otherwise, prior radiation (HR 6.221, CI 1.236–31.314) and cavernous sinus involvement (HR 14.464, CI 3.326–62.901) were negative predictors of PFS. The most common cause of treatment failure was local recurrence. In T4 stage head and neck STS with skull-base involvement, FNCLCC grade, radiation status, and anatomic spread should be considered in determining the overall treatment strategy.

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.

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.

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.

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.

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.