Nationale Des Centres De Lutte Research Articles

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.

Can DNA Methylation Profiling Classify Histologic Subtypes and Grades in Soft Tissue Sarcoma?

A clear classification of the subtype and grade of soft tissue sarcoma is important for predicting prognosis and establishing treatment strategies. However, the rarity and heterogeneity of these tumors often make diagnosis difficult. In addition, it remains challenging to predict the response to chemotherapy and prognosis. Thus, we need a new method to help diagnose soft tissue sarcomas and determine treatment strategies in conjunction with traditional methods. Genetic alterations can be found in some subtypes of soft tissue sarcoma, but many other types show dysregulated gene expression attributed to epigenetic changes, such as DNA methylation status. However, research on DNA methylation profiles in soft tissue sarcoma is still insufficient to provide information to assist in diagnosis and therapeutic decisions. (1) Do DNA methylation profiles differ between normal tissue and soft tissue sarcoma? (2) Do DNA methylation profiles vary between different histologic subtypes of soft tissue sarcoma? (3) Do DNA methylation profiles differ based on tumor grade? Between January 2019 and December 2022, we treated 85 patients for soft tissue sarcomas. We considered patients whose specimens were approved for pilot research by the Human Biobank of St. Vincent's Hospital, The Catholic University of Korea, as potentially eligible. Based on this, 41% (35 patients) were eligible; 1% (one patient) was excluded because of gender mismatch between clinical and genetic data after controlling for data quality. Finally, 39 specimens (34 soft tissue sarcomas and five normal samples) were included from 34 patients who had clinical data. All tissue samples were collected intraoperatively. The five normal tissue samples were from muscle tissues. There were 20 female patients and 14 male patients, with a median age of 58 years (range 19 to 82 years). Genomic DNA was extracted from frozen tissue, and DNA methylation profiles were obtained. Genomic annotation of DNA methylation sites and hierarchical cluster analysis were performed to interpret results from DNA methylation profiling. A t-test was used to analyze different methylation probes. Benjamini-Hochberg-adjusted p value calculations were used to account for bias resulting from evaluating thousands of methylation sites. The most common histologic subtypes were liposarcoma (n = 10) and leiomyosarcoma (n = 9). The tumor grade was Fédération Nationale des Centres de Lutte Contre Le Cancer Grades 1, 2, and 3 in 3, 15, and 16 patients, respectively. DNA methylation profiling demonstrated differences between soft tissue sarcoma and normal tissue as 21,188 cytosine-phosphate-guanine sites. Despite the small number of samples, 72 of these sites showed an adjusted p value of < 0.000001, suggesting a low probability of statistical errors. Among the 72 sites, 70 exhibited a hypermethylation pattern in soft tissue sarcoma, with only two sites showing a hypomethylation pattern. Thirty of 34 soft tissue sarcomas were distinguished from normal samples using hierarchical cluster analysis. There was a different methylation pattern between leiomyosarcoma and liposarcoma at 7445 sites. Using the data, hierarchical clustering analysis showed that liposarcoma was distinguished from leiomyosarcoma. When we used the same approach and included other subtypes with three or more samples, only leiomyosarcoma and myxofibrosarcoma were separated from the other subtypes, while liposarcoma and alveolar soft-part sarcoma were mixed with the others. When comparing DNA methylation profiles between low-grade (Grade 1) and high-grade (Grades 2 and 3) soft tissue sarcomas, a difference in methylation pattern was observed at 144 cytosine-phosphate-guanine sites. Among these, 132 cytosine-phosphate-guanine sites exhibited hypermethylation in the high-grade group compared with the low-grade group. Hierarchical clustering analysis showed a division into two groups, with most high-grade sarcomas (28 of 31) separated from the low-grade group and few (3 out of 31) clustered together with the low-grade group. However, three high-grade soft tissue sarcomas were grouped with the Grade 1 cluster, and all of these sarcomas were Grade 2. When comparing Grades 1 and 2 to Grade 3, Grade 3 tumors were separated from Grades 1 and 2. We observed a different DNA methylation pattern between soft tissue sarcomas and normal tissues. Liposarcoma was distinguished from leiomyosarcoma using methylation profiling. High-grade soft tissue sarcoma samples showed a hypermethylation pattern compared with low-grade ones. Our findings indicate the need for research using methylation profiling to better understand the diverse biological characteristics of soft tissue sarcoma. Such research should include studies with sufficient samples and a variety of subtypes, as well as analyses of the expression and function of related genes. Additionally, efforts to link this research with clinical data related to treatment and prognosis are necessary. Level III, diagnostic study.

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.

Subcutaneous Leiomyosarcoma: An Aggressive Malignancy Portending a Significant Risk of Metastasis and Death.

Subcutaneous leiomyosarcoma (LMS) is a rare, poorly understood variant. The current literature on the subject is sparse, consisting of isolated case reports and small clinicopathologic studies compromised by the inclusion of both its more common and indolent counterpart, cutaneous LMS (atypical intradermal smooth muscle neoplasm), as well as highly aggressive deep-seated tumors. Thus, precise clinicopathologic characterization is limited. Cases of subcutaneous LMS reviewed at the University of Michigan and Cleveland Clinic from 1994 to 2022 were included in this retrospective study. A total of 39 cases were identified. The mean age was 61 years, and the cohort was predominantly male (23/39; 59%). Tumors averaged 4.2cm and most commonly arose on the extremities (32/39; 82%). The majority (38/39; 97%) were diagnosed at an early pathologic stage (pT1 or pT2). Histopathologically, most tumors were well-circumscribed and were assigned a Fédération Nationale des Centers de Lutte Contre le Cancer grade of either 1 or 2 (24/39; 62%). The majority (22/39; 56%) appeared to arise in association with a blood vessel. Of the 36 cases with accessible clinical data and follow-up (mean 34mo, range 0 to 94mo), 12 (33%) were noted to have metastasized, with the lung representing the most common anatomic location. One case recurred locally. Six of 36 patients (17%) died from the disease at an average of 47 months after diagnosis (range 16 to 94mo). Metastasis or death from disease was significantly associated with the Fédération Nationale des Centers de Lutte Contre le Cancer grade ( P =0.0015), the presence of necrosis ( P =0.032), tumor size ( P =0.049), and AJCC tumor stage ( P =0.036). These data demonstrate that subcutaneous LMS are more aggressive than dermal-based tumors and have a prognosis akin to that of deep-seated LMS.

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

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

Results of resection of forearm soft tissue sarcoma

PurposeSoft tissue sarcomas (STS) of the forearm are rare. We aim to assess their oncological and functional outcomes.MethodsWe retrospectively evaluated 34 patients who underwent surgical excision for forearm STS at our institution between 1993 and 2020. We analyzed postoperative Musculoskeletal Tumor Society rating scale (MSTS) and local recurrence-free survival (LRFS), metastasis-free survival, and overall survival (OS) rates. The significance of the following variables was determined: age, sex, histology, tumor size, Fédération Nationale des Centres de Lutte contre le Cancer grade, American Joint Committee on Cancer stage, surgical margin, unplanned excision, metastases upon initial presentation, receipt of chemotherapy, and radiotherapy (RT).ResultsThe postoperative median MSTS score was 28. Bone resection or major nerve palsy was the only factor that influenced MSTS scores. The median MSTS scores in patients with or without bone resection or major nerve palsy were 24 and 29, respectively (P < 0.001). The 5-year LRFS rates was 87%. Univariate analysis revealed that the histological diagnosis of myxofibrosarcoma was the only factor that influenced LRFS (P = 0.047). The 5-year MFS rates was 71%. In univariate analysis, no factors were associated with MFS. The 5-year OS rates was 79%. Age was the only factor that influenced OS (P = 0.01).ConclusionIn the treatment of forearm STS, reconstruction of the skin and tendon can compensate for function, while bone resection and major nerve disturbance cannot. Careful follow-up is important, especially in patients with myxofibrosarcoma, due to its likelihood of local recurrence.

Histological and immunohistochemical prognostic factors of primary angiosarcoma.

Angiosarcoma is a malignant vascular endothelial neoplasm with various histological patterns. Despite its highly malignant potential, histological prognostic prediction has not been adopted for angiosarcoma. This study aimed to establish a method of predicting the prognosis of primary angiosarcoma. Formalin-fixed, paraffin-embedded samples from 104 primary angiosarcomas were prepared. All the cases were reviewed based on histological examinations with H&E staining. Because the French Fédération Nationale des Centres de Lutte Contre Le Cancer system (FNCLCC) is not adopted for angiosarcoma, we experimentally established a modified version of FNCLCC. Immunohistochemical staining for ERG, CD31, CD34, D2-40, HHV-8, p16, C-MYC, and p53 was performed. Fluorescence in situ hybridization (FISH) was performed for 31 cases to assay c-MYC gene amplification. Multivariate analysis revealed that age (> 70years old) (p = 0.0011), non-cutaneous angiosarcoma (p = 0.0265), metastasis on diagnosis (p < 0.0001), size ≥ 5cm (p = 0.0388), no taxane chemotherapy (p = 0.0388), strong nuclear atypia (p = 0.0087), and the presence of luminal structure in ≥ 50% of the tumor volume (p = 0.0009) were independent poor prognostic factors. Among angiosarcomas with luminal formation, mFNCLCC scores were significantly correlated with a poorer prognosis. The overexpression of p16 was associated with less luminal formation (p = 0.0192). Immunohistochemical analysis of C-MYC showed a moderate level of concordance with FISH (Kappa value = 0.45). This study suggested that luminal formation and nuclear atypia may be poor histological prognostic factors of angiosarcoma and that mFNCLCC would be useful for predicting the prognosis of angiosarcoma with luminal formation.

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.

Primary synovial sarcoma on MRI - a case series and review of the literature.

Simple MRI features are mandatory to facilitate the diagnostics of synovial sarcomas, especially for radiolo-gists outside multidisciplinary sarcoma centres. In this case-series and review, we investigate the main appearance of synovial sarcoma on MRI. Fifteen histologically proven primary synovial sarcomas who underwent MRI at 2 different sarcoma centres were included in this case series. Patients and their primary synovial sarcomas were examined for age, localization, mean tumour size (in mm), histological grade (G - according to the Fédération Nationale des Centres de Lutte Contre Le Cancer [FNCLCC]), configuration, T2 signal intensity, presence/absence of "triple sign", heterogeneity/homogeneity, borders (well-defined or infiltrative), and intensity of contrast enhancement on MRI. Additionally, a comprehensive literature review to identify observational studies, reviews, and case-reports assessing MRI features of primary synovial sarcoma was performed. The mean age of the patients was 47.6 years (SD: 17.2). The mean size of primary synovial sarcoma was 59.3 mm (SD: 42). Primary synovial sarcomas were significantly most often multilobulated (n = 12, p < 0.01), heterogeneous (n = 10), and infiltrative (n = 9). Additionally, 3 other primary synovial sarcomas showed the following configurations: ovoid/nodular (n = 2) and fascicular (n = 1). Ovoid/nodular synovial sarcomas were solely depicted as homogeneous with well-defined borders. All tumours showed T2 hyperintense signal and presented with marked contrast enhancement. Primary synovial sarcomas are mainly multilobulated, heterogeneous, and infiltrative tumours. In minor cases, ovoid/nodular or fascicular configurations occur. Knowing the main appearance of synovial sarcoma can help facilitate the diagnostics of primary synovial sarcomas.

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.

Role of Histopathology in diagnosis of Soft Tissue Tumors at Tertiary Care Center

Introduction: Soft tissue tumors (STTs) are a diverse group of neoplasms. It varies from the most common benign tumors to some self-limited lesions and rare malignant soft tissue tumors. Because of the overlap in their clinical and radiological characteristics, histopathology is crucial in determining their diagnosis.&#x0D; Objectives: To study the relative frequencies of types of soft tissue tumors (benign, intermediate and malignant) as well as their histological pattern in relation to age, gender and site of distribution.&#x0D; Methodology: This was a retrospective study conducted over a period of three years from January 2018 to December 2020 in the Department of Pathology, Dhulikhel Hospital, Kavre Nepal. This study included STTs of all the anatomical sites excluding STTs of the female reproductive system. The tumors were classified as benign, intermediate, or malignant using the WHO 2013 classification of soft tissue and bone tumors. The sarcomas were further graded into grades 1, 2, and 3 using the FNCLCC (French Federation Nationale des Centres de Lutte Contre le Cancer) grading system. Immunohistochemistry (IHC) and special staining procedures were also performed as and when required. &#x0D; Result: A total of 198 STTs were studied, of which benign cases were 191 (96.45%), intermediate 03 (1.52%) and malignant 04 (2.03%) in number. The most common type of STTs was vascular tumors 77(38.89%) followed by adipocytic tumors 52(26.26%) and nerve sheath tumors 13(6.56%). STTs were most common in the third decade of life, with the head and neck region being the commonest site. All four malignant tumors were categorized using the FNCLCC grading system. There were three cases of Grade 2 sarcoma and one case of Grade 3 sarcoma.&#x0D; Conclusion: The most common benign tumors were vascular tumors followed by adipocytic tumors and nerve sheath tumors. STTs were most common in the third decade of life. Benign tumors were more common than malignant tumors. In comparison to malignant tumors, benign tumors were found at a younger age group. STTs were found mainly in the head and neck region followed by upper and lower limbs. Despite the fact that molecular diagnostics is gaining popularity in the field of soft tissue tumors, histopathology still remains the gold standard.

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.

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.

Comorbidity, body mass index, and performance status as prognostic factors in older patients with soft-tissue sarcoma

IntroductionSurgery, chemotherapy, and radiotherapy are the treatments for soft tissue sarcoma (STS) similar to those for other cancers. However, treatment is even more difficult in older patients because of aging-related weakness. The influence of aging-associated factors on prognosis in the patients with STS has not been fully elucidated. This study aimed to clarify the factors that impact prognosis in older patients with STS. Materials and MethodsThe present study retrospectively analyzed the data of 262 (≥60 years old) patients with STS. Moreover, this study investigated (1) tumor-associated parameters (e.g., tumor site, tumor size, depth, histological grade [Federation Nationale des Centres de Lutte le Cancer], American Joint Committee on Cancer [AJCC, eighth edition] stage, and histotype); (2) treatment-related factors (i.e., presence of surgery, neoadjuvant/adjuvant chemotherapy, adjuvant radiotherapy, and surgical margin); and (3) patient-dependent counterparts (e.g., age, gender, performance status [PS], body mass index [BMI], and Charlson comorbidity index [CCI]). Statistical analysis was conducted to evaluate the impact of each factor on overall survival (OS). ResultsAmong the 262 patients, 217 and 45 were 60–79 and ≥80 years old, respectively. A comparison of the sociodemographic background showed no significant difference other than surgical margin and PS between those groups. According to univariate analysis, the significant factors to impact OS were age, stage, tumor size, depth, surgical margin, PS, BMI, and CCI. Multivariate analysis indicated that advanced stage, poor PS, and low BMI were negative prognostic factors for OS. Intriguingly, multivariate analysis demonstrated that CCI was a not significant factor for OS in this study. DiscussionWhile AJCC stage is a well-known determinant, this study suggests that physicians should be alerted to poor PS and low BMI in older patients with STS.

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.