Nationale Des Centres De Lutte Research Articles

Effect of Neoadjuvant Chemotherapy Plus Regional Hyperthermia on Long-term Outcomes Among Patients With Localized High-Risk Soft Tissue Sarcoma

ImportancePatients with soft tissue sarcoma are at risk for local recurrence and distant metastases despite optimal local treatment. Preoperative anthracycline plus ifosfamide chemotherapy improves outcome in common histological subtypes.ObjectiveTo analyze whether the previously reported improvement in local progression-free survival by adding regional hyperthermia to neoadjuvant chemotherapy translates into improved survival.Design, Setting, and ParticipantsOpen-label, phase 3 randomized clinical trial to evaluate the efficacy and toxic effects of neoadjuvant chemotherapy plus regional hyperthermia. Adult patients (age ≥18 years) with localized soft tissue sarcoma (tumor ≥5 cm, French Federation Nationale des Centers de Lutte Contre le Cancer [FNCLCC] grade 2 or 3, deep) were accrued across 9 centers (6, Germany; 1, Norway; 1, Austria; 1, United States) from July 1997 to November 2006. Follow-up ended December 2014.InterventionsAfter stratification for tumor presentation and site, patients were randomly assigned to either neoadjuvant chemotherapy consisting of doxorubicin, ifosfamide, and etoposide alone, or combined with regional hyperthermia.Main Outcomes and MeasuresThe primary end point was local progression-free survival. Secondary end points included treatment safety and survival, with survival defined from date of randomization to death due to disease or treatment. Patients lost to follow-up were censored at the date of their last follow-up.ResultsA total of 341 patients were randomized, and 329 (median [range] age, 51 [18-70] years; 147 women, 182 men) were eligible for the intention-to-treat analysis. By December 2014, 220 patients (67%; 95% CI, 62%-72%) had experienced disease relapse, and 188 (57%; 95% CI, 52%-62%) had died. Median follow-up was 11.3 years. Compared with neoadjuvant chemotherapy alone, adding regional hyperthermia improved local progression-free survival (hazard ratio [HR], 0.65; 95% CI, 0.49-0.86; P = .002). Patients randomized to chemotherapy plus hyperthermia had prolonged survival rates compared with those randomized to neoadjuvant chemotherapy alone (HR, 0.73; 95% CI, 0.54-0.98; P = .04) with 5-year survival of 62.7% (95% CI, 55.2%-70.1%) vs 51.3% (95% CI, 43.7%-59.0%), respectively, and 10-year survival of 52.6% (95% CI, 44.7%-60.6%) vs 42.7% (95% CI, 35.0%-50.4%).Conclusions and RelevanceAmong patients with localized high-risk soft tissue sarcoma the addition of regional hyperthermia to neoadjuvant chemotherapy resulted in increased survival, as well as local progression-free survival. For patients who are candidates for neoadjuvant treatment, adding regional hyperthermia may be warranted.Trial Registrationclinicaltrials.gov Identifier: NCT00003052

Clinicopathological and prognostic value of transforming acidic coiled-coil-containing protein 3 (TACC3) expression in soft tissue sarcomas.

Transforming acidic coiled-coil-containing protein 3 (TACC3), a microtubule regulator, is associated with various cancers. However, the relationship between TACC3 and soft tissue sarcomas (STS) remains unclear. We investigated the expression of TACC3 in 136 STS patient samples using immunohistochemical (IHC) staining, and the statistical associations between TACC3 expression and clinicopathological characteristics were evaluated. Additionally, the expression levels of the tumor suppressor p53 and of the cell proliferation marker Ki-67 were also assessed by IHC. High TACC3 expression was detected in 94/136 of STS cases (69.1%), and significantly correlated with higher grade according to the French Fédération Nationale des Centres de Lutte Contre le Cancer system (P<0.0001), poorer tumor differentiation (P<0.0001), increased mitotic counts (P<0.0001), advanced stage per American Joint Committee on Cancer guidelines (P<0.0001), higher p53 expression (P = 0.0487), higher Ki-67 expression (P<0.0001), and undergoing postoperative therapy (P = 0.0001). Disease-free survival (DFS) and overall survival (OS) of patients with high TACC3 expression were significantly shorter (P<0.0001 and P<0.0001, respectively). On multivariate analyses, high TACC3 expression was an independent negative prognostic factor for both DFS and OS (hazard ratio [HR]: 3.074; P = 0.0235 and HR: 8.521; P = 0.0415, respectively). Our results suggest that TACC3 is an independent prognostic factor and may be a novel therapeutic target for the treatment of STS.

A CORRELATIVE STUDY ON SPINDLE CELL SARCOMA WITH CYTO-HISTOLOGICAL GRADING BY CONVENTIONAL METHODS IN AN INDIAN TERTIARY CARE TEACHING HOSPITAL

Objective: Spindle cell sarcomas constitute an important component of soft tissue sarcomas, where accurate grading is more important than histologic subtypes to plan treatment strategies and determine prognosis. To assess whether histologic criteria for grading sarcomas could be applied to fine needle aspiration biopsy (FNAB) specimens of adult spindle cell sarcomas without knowledge of sarcoma subtypes. Furthermore, correlate this grading with histologic Federation Nationale Des Centres de lutte contre le cancer (FNCLCC) grading system and find out the percentage of accuracy of FNAB grading. Methods: Hundred cases were studied by fine needle aspiration cytology (FNAC), among them 50 cases found to be spindle cell sarcoma; in only 42 cases surgical specimens were available. Each aspiration being spread into two or more slides. Subsequently, biopsy was done and studied. Technique used - grading of FNAB specimens and corresponding surgical specimens. Result: Grading of FNAB specimens done taking into account four parameters - nuclear atypia, nuclear variation (nuclear contour, chromatin, nucleoli, and nuclear overlap), mitotic figure, and necrosis. Grading of surgical specimens done by FNCLCC system. The overall results were correlated for both FNAC and biopsy concordance and statistically analyzed. From there the sensitivity and specificity were calculated as 95.23% and 80.76%, respectively. Conclusion: Histologic criteria for grading sarcomas in adults could be applied to FNAC specimens of spindle cell sarcomas with 88% accuracy. While comparing the diagnosis given by FNAC and biopsy, it revealed the true positive were 40 cases, true negative 42 cases, false positive 10 cases, and false negative (FN) 2 cases.

Clinicopathologic study of cardiac myxofibrosarcomas

Objective: To investigate the clinicopathologic features of cardiac myxofibrosarcomas. Methods: The clinical data, pathomorphologic and immunohistochemical features were evaluated in five cases of cardiac myxofibrosarcoma collected from January 2009 to December 2014, with relevant literature review. Results: Five patients with cardiac myxofibrosarcoma, including four women and one man [age range 39-61 years; mean (50.4±9.0) years] were included. All tumors were broadbased and located mainly in the left atrium, with one case extending through the atrial wall and pericardium to the left lower lung lobe. The morphological grade was low in one case, intermediate in one, and high in three. Using Fédération Nationale des Centres de Lutte Contre le Cancer (FNLCC) grading system, one case was grade 1 and four cases were grade 2. Immunohistochemical analysis revealed diffuse and strong expression for vimentin in all cases. Smooth muscle actin and muscle specific actin were variably expressed. Complete tumor excision was performed in one case, and tumor debulking was performed in the other four cases. Clinical follow-up was available in three cases. One patient with en bloc excision of the tumor mass survived 13 months and the other two with tumor debulking died one month after surgery. Conclusions: The most common location for cardiac myxofibrosarcoma is the left atrium. Some myxofibrosarcoma may be histologically bland and misdiagnosed as myxoma due to histological similarities. Thus caution should be exercised in their microscopic differentiation. Precise imaging, multidisciplinary approach and adequate initial surgery may contribute to improving the clinical outcomes of myxofibrosarcoma.

Histopathological Spectrum of Soft-Tissue Tumors with Immunohistochemistry Correlation and FNCLCC grading: A North Indian Experience.

Introduction:Soft tissue tumors (STT) are mesenchymal neoplasms with a diverse spectrum and overlapping clinical, radiological and histological features. Histopathology and immunohistochemistry (IHC) are essential to make a diagnosis. Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) Sarcoma Group grading system based on tumour differentiation, mitotic rate and necrosis helps in predicting the tumour progression and treatment response.Aims:The goal of this study was to analyze the incidence, histological spectrum and IHC features of STTs and to grade sarcomas according to FNCLCC grading system.Material and Methods:This is a four year study conducted in the Department of Pathology of a tertiary care centre from July 2009 to June 2013. All histopathologically diagnosed STTs were evaluated for gross and microscopic appearance. IHC was done wherever needed and clinical correlation was attempted. Sarcomas were graded according to FNCLCC grading system.Results:Of the total 270 cases studied, benign, intermediate and malignant STTs were 67.0%, 7.0% and 25.9% respectively. Adipocytic, vascular and peripheral nerve sheath tumors (PNST) formed the bulk of overall STTs (34.1%, 18.5% and 11.1% respectively). Sarcomas not otherwise specified were found to be the most common soft-tissue sarcomas followed by smooth muscle sarcomas and tumors with uncertain differentiation (11.5%, 4.1%, and 3.3%, respectively). Benign STTs were seen two decades earlier and were superficial in location as compared to sarcomas. On FNCLCC grading, grade 3 soft tissue sarcomas were slightly higher in number than grade 2 (27 vs 24). On IHC a definitive diagnosis was reached in 33 malignant, all intermediate and nine benign cases.Conclusion:The incidence of intermediate and malignant STTs is increasing due to early detection and better diagnosis by ancillary techniques like IHC. FNCLCC grading helps to prognosticate the malignant STTs thus guiding further plan of action while in some tumors like MPNST and Angiosarcoma it has no prognostic significance.

Myxofibrosarcoma of the extremity and trunk: a multidisciplinary approach leads to good local rates of LOCAL control.

Myxofibrosarcomas (MFSs) are malignant soft-tissue sarcomas characteristically presenting as painless slowly growing masses in the extremities. Locally infiltrative growth means that the risk of local recurrence is high. We reviewed our experience to make recommendations about resection strategies and the role of the multidisciplinary team in the management of these tumours. Patients with a primary or recurrent MFS who were treated surgically in our unit between 1997 and 2012 were included in the study. Clinical records and imaging were reviewed. A total of 50 patients with a median age of 68.4 years (interquartile range 61.6 to 81.8) were included. There were 35 men; 49 underwent surgery in our unit. The lower limb was the most common site (32/50, 64%). The mean size of the tumours was 8.95 cm (1.5 to 27.0); 26 (52%) were French Fédération Nationale des Centres de Lutte Contre le Cancer grade III. A total of 21 (43%) had positive margins after the initial excision; 11 underwent further excision. Histology showed microscopic spread of up to 29 mm beyond macroscopic tumour. Local recurrence occurred in seven patients (14%) at a mean of 21 months (3 to 33) and 15 (30%) developed metastases at a mean of 17 months (3 to 30) post-operatively. High rates of positive margins and the need for further excision makes this tumour particularly suited to management by multidisciplinary surgical teams. Microscopic tumour can be present up to 29 mm from the macroscopic tumour in fascially-based tumours. Cite this article: Bone Joint J 2016;98-B:1682-8.

Malignant Peripheral Nerve Sheath Tumor Is a Challenging Diagnosis: A Systematic Pathology Review, Immunohistochemistry, and Molecular Analysis in 160 Patients From the French Sarcoma Group Database.

An accurate histopathologic diagnosis is essential for an adequate treatment of soft tissue sarcomas. The diagnosis of malignant peripheral nerve sheath tumor (MPNST) can be complex, particularly outside the neurofibromatosis type 1 (NF1) context. MPNST is a rare malignancy, and due to the lack of specific histologic criteria, several differential diagnoses must be considered. A total of 350 patients diagnosed with MPNST (from 1990 to 2013) were retrieved from the French sarcoma network (RRePS) and the Conticabase (Connective Tissue Cancer Network database). Tumor samples were available for 160 cases (45.2%). Pathology review, immunohistochemistry (IHC), and molecular analysis (when dealing with a monomorphic sarcoma) were systematically performed. Patient, tumor, and treatment characteristics were evaluated to identify prognostic factors for the definitive primary MPNST (n=106) cohort. Twenty-nine tumors (18.1%) initially diagnosed as MPNST were reclassified on the basis of histologic review, IHC, and molecular analysis. Patients with NF1 disease comprised 64% of the remaining cohort. The 5-year overall survival for patients from the entire cohort was 47%, 34.8% for NF1 patients, and 68.5% for patients without NF1 disease, making NF1 syndrome an independent poor prognostic factor of survival. Positive margins and lack of radiation therapy were independent predictors of local recurrence. The Fédération Nationale des Centres de Lutte Contre le Cancer tumor grade was an independent prognostic indicator of metastasis. Given the therapeutic implications of a misdiagnosis, the systematic pathology review, IHC, and molecular analysis (when dealing with monomorphic sarcoma) strategy allowed reclassification of 20% of cases, mainly the sporadic MPNSTs.

Federation Nationale des Centers de Lutte Contre le Cancer grading of soft tissue sarcomas on needle core biopsies using surrogate markers

Needle core biopsy (NCB) of soft tissue sarcomas (STSs) presents problems for French Federation Nationale des Centers de Lutte Contre le Cancer (FNCLCC) histological grading because small sample size hinders determination of necrosis and mitotic activity. We graded 53 STSs on NCB using a modified FNCLCC grading system that substitutes Ki-67 immunoexpression for mitotic count and uses a radiological assessment of necrosis, and compared the results with those obtained by conventional FNCLCC grading of the corresponding untreated, surgically resected specimen. Forty-eight of the 53 tumors were classified as malignant on NCB (concordance = 91%). The modified FNCLCC grade correctly separated high-grade (grades II and III) from low-grade sarcomas in 70% of cases and predicted the traditional FNCLCC grade given to the resected specimen in 49% of cases. Ki-67 scores of 2 or 3 were observed in 5 tumors classified as low-grade neoplasms on NCB but upgraded to a high-grade dedifferentiated liposarcoma on resection. Underestimated NCB grades were commonly encountered with lipomatous tumors due to sampling error, whereas Ki-67 or radiologic necrosis scores higher than the corresponding histological scores were responsible for the vast majority of overestimated NCB grades. Our FNCLCC grading scheme replacing conventional mitosis counting and histologic assessment of necrosis with surrogate markers is useful in separating high- and low-grade STSs on NCB for STS treatment planning. High Ki-67 rate should raise suspicion of a higher-grade component, particularly with fatty tumors.

RNA sequencing validation of the Complexity INdex in SARComas prognostic signature

BackgroundPrognosis of metastatic outcome in soft tissue sarcomas is an important clinical challenge since these tumours can be very aggressive (up to 50% of recurring events). A gene expression signature, Complexity INdex in SARComas (CINSARC), has been identified as a better prognostic factor compared to the current international grading system defined by the Fédération Nationale des Centres de Lutte Contre le Cancer. Since CINSARC has been established on frozen tumours analysed by microarrays, we were interested in evaluating its prognostic capacity using next generation sequencing (NGS) on formalin-fixed, paraffin-embedded (FFPE) blocks to better fit laboratory practices. MethodsMetastatic-free survivals (training/validation approach with independent datasets) and agreement values in classification groups were evaluated. Also, RNA degradation threshold has been established for FFPE blocks and differences in gene expression due to RNA degradation were measured. ResultsCINSARC remains a strong prognostic factor for metastatic outcome in both microarray and RNA-seq technologies (P < 0.05), with similar risk-group classifications (77%). We defined quality threshold to process degraded RNA extracted from FFPE blocks and measured similar classifications with frozen tumours (88%). ConclusionThese results demonstrate that CINSARC is a platform and material independent prognostic signature for metastatic outcome in various sarcomas. This result opens access to metastatic prognostication in sarcomas through NGS analysis on both frozen and FFPE tumours via the CINSARC signature.

Chondroitin sulfate synthase 1 expression is associated with malignant potential of soft tissue sarcomas with myxoid substance

The glycosyltransferases chondroitin sulfate synthase 1 (CHSY1) and exostoses-like 3 (EXTL3) specifically function in biosynthesis of the glycans chondroitin sulfate and heparan sulfate, respectively. Although these glycans play important roles in pathogenesis of various tumors, their significance in soft tissue sarcoma remains unknown. Here, we asked whether CHSY1 or EXTL3 expression correlates with malignant potential of soft tissue sarcomas with myxoid substance. To do so, we examined 40 samples representing specific types, including 12 cases of myxoid liposarcoma, 14 of myxofibrosarcoma, 12 of malignant peripheral nerve sheath tumor, and 2 of low-grade fibromyxoid sarcoma. We performed immunohistochemistry with anti-CHSY1 and anti-EXTL3 antibodies and compared enzyme expression levels with tumor histologic grade as assessed by the Fédération Nationale des Centres de Lutte Contre le Cancer classification and with patient 5-year survival rate. CHSY1 and EXTL3 were expressed in 72.5% and 32.5% of all tumors, respectively. Notably, CHSY1 was strongly expressed in myxofibrosarcoma and malignant peripheral nerve sheath tumor compared with other tumors and significantly associated with higher- rather than lower-grade tumors (P < .01). High expression of CHSY1 was also significantly associated with poorer patient outcomes (P = .031) and higher stages assessed by American Joint Committee on Cancer staging system (P = .004). By contrast, EXTL3 expression was not correlated with histologic grade or patient prognosis. We conclude that CHSY1 expression is closely associated with malignant potential of soft tissue sarcomas with myxoid substance.

Primary leiomyosarcoma of the pancreas: report of a case treated by local excision and review of the literature.

BackgroundFirst described by Ross in 1951, primary pancreatic leiomyosarcoma is a rare mesenchymal tumour of the pancreas, with nonspecific clinical and radiological features and a poor prognosis, if unresectable.Case reportA 60-year-old woman presented with abdominal pain. Magnetic resonance imaging (MRI) and computed tomography (CT) scan detected a dishomogeneous egg-shaped 8-cm mass, arising from the pancreatic head, with duodenal compression, without dilation of the Wirsung duct. 18F-FDG positron-emission tomography (PET)-CT showed a moderate tracer uptake, and the endoscopic ultrasound (US) showed a hypoechoic lesion, arising from the duodenal wall, suspected to be a gastrointestinal stromal tumour (GIST). CEA, CA19-9, NSE, and chromogranin A were normal. At the surgical exploration, a 10-cm mass, adherent to the anterior aspect of the pancreatic head, was found. The lesion was easily separable from the duodenal wall and was totally excised. The frozen intraoperative examination showed a mesenchymal tumour, with spindle-shaped cells, suggesting that a GIST diagnosis was likely. Postoperative course was uneventful. Histology and immunohistochemistry demonstrated a well-differentiated leiomyosarcoma, with five to six mitotic counts per 10 high-power field (HPF) and proliferative index (MIB-1) 10 % (grade 2 according to Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC)), with positive smooth muscle actin, desmin, and caldesmon but negative CD117 (c-kit) and S-100. The patient is alive and asymptomatic 19 months after surgery, without evidences of disease.ConclusionsIn the English literature, only 44 cases of primary pancreatic leiomyosarcoma have been reported. If a pancreatic mass suspected for primary pancreatic leiomyosarcoma has no adjacent organ/vessel invasion or distant metastases, surgical resection is the therapy of choice.

Prognostic factors in patients with recurrent or metastatic retroperitoneal leiomyosarcoma

Factors that predict the prognosis of patients with recurrent or metastatic retroperitoneal leiomyosarcomas after treatment are uncertain. Clinical and pathological data on 22 patients with retroperitoneal leiomyosarcomas who were treated by a multidisciplinary abdominal soft-tissue tumor group were analyzed retrospectively to identify prognostic factors for their progression-free survival (PFS). The median PFS in the 22 patients was 9 months. Microvessel density in tumor tissues, which was evaluated via CD34 expression in 16 cases, and the presence of metastasis on admission were both found to be correlated with PFS in a Kaplan-Meier analysis, but not in a multivariate analysis. The multivariate analysis did, however, show that complete resection of tumors and the FNCLCC (Fédération Nationale des Centres de Lutte Contre Le Cancer) disease grade were independent factors predicting PFS.

Prognostic relevance of Fédération Nationale des Centres de Lutte Contre le Cancer grade and MDM2 amplification levels in dedifferentiated liposarcoma: a study of 50 cases

Dedifferentiated liposarcoma represents a form of liposarcoma composed of a non-lipogenic sarcoma associated with well-differentiated liposarcoma. The prognostic significance of histological grading of the dedifferentiated component remains to be elucidated due to vague grading criteria employed in previous studies. Molecular markers of tumor behavior, including amplification levels of murine double minute-2 (MDM2) and cyclin-dependent kinase-4 (CDK4) genes, have been explored in a limited number of cases. Here we investigate whether ‘Fédération Nationale des Centres de Lutte Contre le Cancer' (FNCLCC) grade and MDM2 gene amplification levels have prognostic value in dedifferentiated liposarcoma in terms of local recurrence and disease-specific survival. Fifty cases were retrieved, reviewed and FNCLCC grade was scored for the dedifferentiated component. Testing for MDM2 gene amplification was performed by fluorescence in situ hybridization. Amplification was categorized as high level (≥20 copies) and as low level (<20 copies). Follow-up data was obtained through chart review. Log-rank test and Cox proportional hazard models were used to determine the effect of grade and level of MDM2 amplification on outcomes. Our series includes 50 patients (male n=28, female n=22) with an average age of 63 years (range, 28–88) and a median follow-up of 28 months (range, 2–120). Tumors were graded as grade 1 (6%), grade 2 (58%), and grade 3 (36%). When adjusted for age, sex, site, tumor size, and margin status, grade 3 patients had a higher recurrence rate than grades 1 and 2 (HR=2.07, 95% CI: 1.24, 7.62; P=0.015). Patients with high-level MDM2 amplification had higher recurrence rate on univariate analysis (P=0.028), but not on multivariate analysis (HR=1.69, 95% CI: 0.73, 3.94; P=0.221). FNCLCC grade 3 dedifferentiation confers a worse prognosis in dedifferentiated liposarcoma in terms of local recurrence. MDM2 amplification level remains a useful diagnostic tool in dedifferentiated liposarcoma, but has no prognostic value in terms of local recurrence.

Typing and Grading of Soft Tissue Tumors and their Correlation with Proliferative Marker Ki-67

Aim and Objective: The main aim of this study is to categorize, type, grade of soft tissue tumors & correlate it with Ki-67 proliferative index. Material and Methods: The present study was conducted in the Department of Pathology, PGIMS, Rohtak. The study group comprised of excised 44 cases of STT (soft tissue tumors) specimens. Tumor grade was assigned based on the FNCLCC (Federation Nationale des Centers de Lutte Contre le Cancer) grading system. According to the Ki-67 index the patients were divided into two groups: high index group (>50/10HPF) and low index group (<50/10HPF). These grades were correlated with proliferative activity using Ki-67 index. Results: Out of 44 soft tissue tumors in our study 12 (27.27%) were diagnosed as benign and 32 (72.72%) were diagnosed as malignant soft tissue tumors. Average size of benign tumors was 4.50 cm and that of malignant tumors was 10.33 cm. Maximum number of soft tissue tumor were located in the extremities i.e.10 (22.72%) in upper extremity and 24 (54.54%) in the lower extremity. The commonest site affected was thigh (18.2%). Out of the 32 cases of (STS) soft tissue sarcomas, 15 (46.87%) were Grade 2, 13 (40.63%) were Grade 3 and 4 (12.5%) were Grade 1. MPNST (malignant peripheral nerve sheath tumor) had the largest number of cases with Grade 3 (31.3%). All the benign STT had low Ki-67 index, while the Ki-67 index was low in 12 STS and high in 20 STS. The size as well as grade of the tumors showed a significant correlation with Ki-67 index. Conclusion: Grading based on assessment of morphologic variables is one of the most important factors for predicting the prognosis of the patients with STS. Therefore, it should be a part of the pathology report and should be adapted to the modern management of patients.

Fibrosarcoma of the temporomandibular joint area: benefits of magnetic resonance imaging and computed tomography

Here, we report a case of primary fibrosarcoma in the mandible of a 33-year-old woman with symptoms and radiologic signs mimicking temporomandibular disorder. We also present a literature review of fibrosarcomas in the jaw. CASE REPORT A 33-year-old woman presented with a 1-year history of trismus associated with a clicking noise in the left temporomandibular joint (TMJ). Her chin shifted to the right side when she opened her mouth (Figure 1). Panoramic radiographs (Figure 2, A, B) and magnetic resonance imaging (MRI) scans (Figure 3, A-H) of the TMJ regions showed signs of temporomandibular disorder (TMD), so conventional treatment for TMD was prescribed, including occlusal splints, mouth-opening exercises, and a muscle relaxant for 6 months. When the MRI scout images were analyzed retrospectively, the findings of 2 of 5 scout images were suggestive of tumor (see Figure 3, A, E). The patient was referred again 6 months after the initial visit for investigation of insomnia caused by spontaneous pain in the left TMJ area. She also had paralysis of the lower lip and left chin. She had herpes labialis and gastroenteritis caused by stress. Given the suspicion of malignancy, both MRI and computed tomography (CT) were performed. MRI showed a round, inhomogeneous mass in the pterygomandibular portion of the masticator space, which caused minimal medial narrowing of the left parapharyngeal space (Figure 4, A, B). CT found significant bony erosion of the inner cortex of the left ramus of the mandible (Figure 5). The patient was referred to another hospital for further management because the tumor grew toward the pharyngeal arches. An incisional biopsy was subsequently performed, and the initial diagnosis was a sarcoma based on the histopathologic examination of the biopsy. A definitive histologic diagnosis was reached by exclusion. The tumor was diagnosed as a grade 3 (poorly differentiated) fibrosarcoma using the FNCLCC (Federation Nationale des Centres de Lutte Contre le Cancer) grading system. Histopathologic examination found that the tumor contained spindle cells arranged in compact fascicles that were intersected by various amounts of delicate thin to dense keloid-like collagen. Cell bundles were arranged at acute angles to each other, whereas the presence of fascicles was subtler in other areas. A prominent storiform pattern was not seen (Figure 6). The fibrosarcoma was resected followed by postoperative radiotherapy and chemotherapy. The tumor was removed, along with the left ramus of the mandible, a portion of the left maxilla, a deep part of the parotid gland, and lymph nodes located superior to the omohyoid muscle. The cheek mucosa was reconstructed using a free anterolateral thigh flap (Figure 7). The patient recovered and got married afterward; however, lung metastasis with Fig. 1. Facial photograph. The patient’s chin shifted to the right side when she opened her mouth.

Predictors of local recurrence and survival in primary retroperitoneal leiomyosarcoma

To investigate the predictors of local recurrence and survival in primary retroperitoneal leiomyosarcoma (PRLS). A retrospective analysis was conducted on 46 cases of PRLS between August 2006 and April 2012. There were 9 male and 37 female patients, and they were 30-79 year old (median 49 year old). Kaplan-Meier estimations and Cox regression analyses were performed. The tumor size were 5-36 cm, and 29 cases (63.1%) of this group was more than 10 cm. Local 3- and 5-year control rates after complete resection were 47% and 30%. FNCLCC (Fédération Nationale des Centres de Lutte Contre le Cancer) grading (RR = 3.10, 95%CI: 1.59-6.04), gender (RR = 5.30, 95%CI: 1.64-17.13) and blood loss (RR = 3.12, 95%CI: 1.28-7.60) were independent prognostic factor of local recurrence in multivariable analysis (P < 0.05). The 5-year disease-free survival rates after complete resection of PRLS was 26%; and the 5-year disease-specific survival (DSS) rates after complete resection was 48%. The median DSS was 60 months in negative margin of resection and 50 months in positive margin. However, by multivariate analysis, only FNCLCC grading was significant independent predictors of DSS (RR = 2.01, 95%CI: 1.16-3.49, P = 0.013). Gender, FNCLCC grading and blood loss were independent prognostic factor of local recurrence. The disease-specific survival in PRLS varied significantly according to FNCLCC grading.

Histologic variability and diverse oncologic outcomes of prostate sarcomas.

PurposePrimary prostate sarcomas are a rare type of prostate cancer that account for less than 0.1% of primary prostate malignancies. We analyzed the experience of a single institution with prostate sarcoma over 20 years.Materials and MethodsIn this case series, the medical records of 20 patients with prostate sarcoma were reviewed from June 1990 to December 2013 to identify symptoms at presentation, diagnostic procedures, metastasis presence and development, histologic subtype, French Fédération Nationale des Centres de Lutte Contre le Cancer grade, primary tumor grade and size, and treatment sequence, including surgery and preoperative and postoperative therapies. The average follow-up period was 23.6 months (range, 1.4-83.3 months).ResultsThe average patient age was 46.3±16.7 years. Most patients presented with lower urinary tract symptoms (55%). The histologic subtype was spindle cell sarcoma in five patients (25%), rhabdomyosarcoma in three patients (15%), synovial sarcoma in three patients (15%), liposarcoma in three patients (15%), stromal sarcoma in three patients (15%), and Ewing sarcoma, nerve sheath tumor, and adenocarcinoma with sarcomatoid component (5% each). For liposarcoma, two patients were alive after complete surgical resection and had a good prognosis. At last follow-up, 15 patients had died of sarcoma. The 2- and 5-year actuarial survival rates for all 20 patients were 53% and 12%, respectively (medial survival, 20 months).ConclusionsThe disease-specific survival rate of prostate sarcoma is poor. However, sarcoma that is detected early shows a better result with proper management including surgical intervention with radio-chemotherapy than with no treatment. Early diagnosis and complete surgical resection offer patients the best curative chance.

What make differences in the outcome of adjuvant treatments for resected gastric cancer?

After a long history of Dark Age of adjuvant chemotherapy for gastric cancer, definite evidences of survival benefit from adjuvant treatment have been reported since 2000s. These survival benefits are likely attributed to something new approach different from pervious studies. In 2001, South West Oncology Group INT0116 trial yielded survival benefit in curatively resected gastric cancer patients with postoperative chemoradiotherapy [5-fluorouracil (5-FU) + Leucovorin + radiotherapy], followed by positive result by MAGIC Trial, employing peri-operative(pre- and postoperative chemotherapy with Epirubicin, cisplatin (CDDP), 5-fluorouracil (ECF) regimen in patients with curative resection. A novel drug [S1: ACTS-GC (Adjuvant chemotherapy trial of TS-1 for gastric cancer) in 2007], or new drug combination chemotherapys [CDDP + 5-FU: FNCLCC/FFCD (Federation Nationale des Centres de Lutte contre le cancer/Federation Francophone de Cancerologie Digestive) in 2011, Capecitabine + Oxaliplatin: CLASSIC in 2012] also produced positive results in terms of improved prognosis. Neoadjuvant or perioperative chemotherapy, novel anti-cancer drugs, and chemoradiotherapy might be the key words to develop further improvement in the adjuvant treatment of resectable gastric cancer. Moreover, it is not new but still true to stress the importance of D2 surgery as the baseline treatment in order to minimize the amount of residual tumor after surgery.

How Long Should We Follow Patients With Soft Tissue Sarcomas?

Guidelines suggest that followup for low-grade soft tissue sarcomas should be every 3 to 6 months for 2 to 3 years and then annually, and for high-grade sarcomas every 3 to 6 months for 2 to 5 years, then every 6 months for the next 2 years, and then annually. However, there is only very limited evidence to support these strategies. In a population of patients treated surgically for soft tissue sarcomas, we evaluated the (1) timing of diagnosis of local recurrences after sarcoma excision; (2) timing of diagnosis of distant metastases; and (3) the difference in those parameters based on tumor size and grade. Patients diagnosed with soft tissue sarcomas and who underwent surgical excision between 1978 and 2008 were retrospectively reviewed. Age, histologic diagnosis, Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grade, tumor location, and size were reviewed at a mean of 6 years (range, 1 month to 30 years). We met with patients every 3 months for 5 years, every 6 months for 10 years, and then annually until 15 years after surgery. Eight hundred sixty-seven patients with a median age at diagnosis of 52 years were eligible for analysis. The incidence of local recurrence and metastases was calculated for every 2-year period and presented per 1000 person-years. Ninety-eight patients (11%) developed local recurrence at a median time of 19 months; 90% of patients who had local recurrences had them within 7.1 years, and 95% occurred by 8.6 years. One hundred ninety-eight patients (23%) developed distant metastases at a median time of 12 months; 90% of patients who developed metastases developed them by 4.2 years and 95% did so by 7.3 years. High-grade tumors had a higher incidence of local recurrence and metastases in first 2 years, whereas low-grade tumors recurred at a constant rate throughout the followup period. Followup beyond 10 years does not yield a sufficient number of local recurrences or metastases to warrant further monitoring. Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

Prognostic Factors and Outcomes of Patients with Myxofibrosarcoma

Myxofibrosarcomas (MFS) are a historically heterogeneous group of tumors that exhibit a propensity for local recurrence. The objectives of this study were to analyze the prognostic factors and outcomes of patients with MFS treated at a single institution. We retrospectively reviewed the records of 69 consecutive patients with pathologically confirmed MFS of the extremities or superficial trunk who underwent surgery from August 1995 to November 2010. Clinicopathologic features, treatments, and patient outcomes were reviewed. Sixty-nine patients were identified, of whom 38 were men (55%). The median age was 62 years. Sixty-four patients (93%) presented with primary tumors, and 5 patients (7%) presented with locally recurrent tumors. Median tumor size was 6.0 cm, and 44 patients (64%) had grade 3 tumors (FNCLCC [Fédération Nationale des Centres de Lutte Contre le Cancer] classification). Margins were microscopically positive in 14 patients (20%) and negative in 55 patients (80%), including close margins (<1 mm) in 14 patients (20%). Fifty-three patients (77%) received radiotherapy. At a median follow-up of 41 months, there were 11 local (16%) and 11 distant (16%) recurrences. The local and distant 5-year recurrence-free survival rates were 72% and 82%, and the 5-year overall survival was 61%. Increased age (scaled by 0.1; hazard ratio [HR] 1.80, P=0.002) and tumor size (HR 1.12, P=0.004) were negatively correlated with overall survival. Positive/close (<1 mm) margin status (HR 4.34, P=0.030) predicted worsened local recurrence-free survival. MFS exhibit a propensity for local recurrence, which is predicted by resection with positive or close margins. Aggressive surgery combined with radiotherapy may contribute to more effective local control.