Phase II clinical trial of pazopanib for patients with unresectable or metastatic malignant peripheral nerve sheath tumors.

Malignant peripheral nerve sheath tumor (MPNST) often does not respond well to chemotherapy and develops against a background of NF1. The purpose of our study was to examine the efficacy of pazopanib against MPNST. Our study was designed as a physician-initiated phase II clinical trial in patients with advanced MPNST. Patients were registered from 11 large hospitals. The primary endpoint was set to clarify the clinical benefit rate (CBR) at 12 weeks according to response evaluation criteria in solid tumors (RECIST). Progression-free survival (PFS), overall survival (OS) and the CBR based on modified Choi evaluation at week 12 were set as secondary endpoints along with treatment-related safety. The study enrolled 12 patients. Median age was 49 years. Seven had Grade 2 and five Grade 3 according to the FNCLCC evaluation. Median follow-up period was 10.6 months. CBR at 12 weeks was both 50.0% (RECIST and Choi). The median PFS was 5.4 months for both RECIST and Choi, and the median OS was 10.6 months. Of special interest, the median PFS was 2.9 months for patients with FNCLCC Grade 2 and 10.2 months for Grade 3 (both RECIST and Choi). Grade 4 adverse events of neutropenia and lipase elevation were noted in one patient each. The results of this pazopanib therapy were generally better than those of any of the other single molecular targeted therapies reported previously. Although accumulation of more cases remains necessary, we conclude pazopanib treatment for MPNST to be a safe and promising treatment after doxorubicin-based chemotherapy.

Incidence and prognosis of distant metastasis in malignant peripheral nerve sheath tumors.

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are a type of soft tissue sarcomas (STS) with recurrence and metastatic potential. We aimed to investigate the risk factors for developing distant metastases (DM) and to identify the prognostic factors in patients with DM. METHODS: Based on the Surveillance, Epidemiology, and End Result (SEER) database, MPNST patients diagnosed between 2010 and 2016 were extracted in our study. The logistic regression model was performed for predicting DM development while the Cox proportional hazard regression model was conducted for revealing the prognostic factors. RESULTS: Eventually, 764 patients diagnosed with MPNSTs were included with 109 cases presenting with metastases at initial diagnosis. Larger tumor size and lymph node metastases were independent risk factors for developing DM. The median overall survival (OS) for patients with metastases was 8.0 (95% CI: 6.1-9.9) months. Multiple metastatic sites and no surgical treatment were prognostic factors for worse survival. Tumors located in non-head and neck region were related with better survival. CONCLUSIONS: The incidence of DM was 14.3% with a dismal median OS of 8.0 months for metastatic MPNSTs. More evaluation should be applied for patients with large tumor size and lymph metastases. Tumors located in head and neck region and the presence of multiple metastases predicted worse survival outcome. Surgical treatment can significantly improve the survival of MPNST patients with distant metastasis.

Neurofibromatosis-associated malignant peripheral nerve sheath tumors in children have a worse prognosis: A nationwide cohort study.

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNST) are rare and aggressive non-rhabdomyoblastic soft-tissue sarcomas (NRSTS) in children. This study set out to investigate clinical presentation, treatment modalities, and factors associated with survival in pediatric MPNST using Dutch nationwide databases. METHODS: Data were obtained from the Netherlands Cancer Registry (NCR) and the Dutch Pathology Database (PALGA) from 1989 to 2017. All primary MPNSTs were collected. Demographic differences were analyzed between adult and pediatric (age ≤18 years) MPNST. In children, demographic and treatment differences between neurofibromatosis type 1 (NF1) and non-NF1 were analyzed. A Cox proportional hazard model was constructed for localized pediatric MPNSTs. RESULTS: A total of 70/784 MPNST patients were children (37.1% NF1). Children did not present differently from adults. In NF1 children, tumor size was more commonly large (> 5 cm, 92.3% vs 59.1%). Localized disease was primarily resected in 90.6%, and radiotherapy was administered in 37.5%. Non-NF1 children tended to receive chemotherapy more commonly (39.5% vs 26.9%). Overall, estimated five-year survival rates of localized NF1-MPNST was 52.4% (SE: 10.1%) compared with 75.8% (SE: 7.1%) in non-NF1 patients. The multivariate model showed worse survival in NF1 patients (HR: 2.98; 95% CI, 1.17-7.60, P = 0.02) and increased survival in patients diagnosed after 2005 (HR: 0.20; 95% CI, 0.06-0.69, P = 0.01). No treatment factors were independently associated with survival. CONCLUSION: Pediatric MPNSTs have presentations similar to adult MPNSTs. In children, NF1 patients present with larger tumors, but are treated similarly to non-NF1 MPNSTs. In localized pediatric MPNST, NF1 is associated with worse survival. Promisingly, survival has increased for pediatric MPNSTs after 2005.

A Phase II Trial of Sorafenib and Dacarbazine for Leiomyosarcoma, Synovial Sarcoma, and Malignant Peripheral Nerve Sheath Tumors.

BACKGROUND: Sorafenib and dacarbazine have low single-agent response rates in metastatic sarcomas. As angiogenesis inhibitors can enhance the efficacy of chemotherapy, we investigated the combination of sorafenib and dacarbazine in select sarcoma subtypes. MATERIALS AND METHODS: Patients with leiomyosarcoma (LMS), synovial sarcoma (SS), or malignant peripheral nerve sheath tumors (MPNST) with up to two previous lines of therapy and adequate hepatic, renal, and marrow function received 3-week cycles of sorafenib at 400 mg oral twice daily and dacarbazine 1,000 mg/m2 intravenously (later reduced to 850 mg/m2). Patients were evaluated for response every 6 weeks. The primary objective was to determine the disease control rate (DCR) of sorafenib plus dacarbazine in the selected sarcoma subtypes. RESULTS: The study included 37 patients (19 female); median age was 55 years (range 26-87); and histologies included LMS (22), SS (11), and MPNST (4). The DCR was 46% (17/37). Median progression-free survival was 13.4 weeks. The RECIST response rate was 14% (5/37). The Choi response rate was 51% (19/37). Median overall survival was 13.2 months. Of the first 25 patients, 15 (60%) required dacarbazine dose reductions for hematologic toxicity, with one episode of grade 5 neutropenic fever. After reducing the starting dose of dacarbazine to 850 mg/m2, only 3 of the final 12 (25%) patients required dose reduction. CONCLUSION: This phase II study met its primary endpoint with an 18-week DCR of 46%. The clinical activity of dacarbazine plus sorafenib in patients with these diagnoses is modest. IMPLICATIONS FOR PRACTICE: Metastatic soft tissue sarcomas are a heterogeneous group of relatively rare malignancies. Most patients are treated with cytotoxic chemotherapy or targeted therapy in the form of tyrosine kinase inhibitors. Response rates are relatively low, and there is a need for better therapies. This clinical trial demonstrates that combining a cytotoxic therapy (dacarbazine) with an antiangiogenic small molecule (sorafenib) is feasible and associated with favorable disease-control rates; however, it also increases the potential for significant toxicity.

Nomograms for predicting the overall and cause-specific survival in patients with malignant peripheral nerve sheath tumor: a population-based study.

BACKGROUND: Malignant peripheral nerve sheath tumor (MPNST) is extremely rare in soft tissue sarcoma, with a high rate of recurrence and metastasis. Due to its rarity, the epidemiological features and prognostic factors are still uncertain. Moreover, nomograms for patients with MPNST have not been constructed and validated until now. PATIENTS AND METHODS: Patients diagnosed with MPNST between 1973 and 2014 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Survival analysis, machine learning and Lasso regression were used to identify the prognostic factors for overall survival (OS) and cause-specific survival (CSS). Significant prognostic factors were integrated to construct nomograms and then the nomograms were validated externally with a separate cohort from our own institution. RESULTS: A total of 689 patients were included in the training set and 42 patients in the validation set. Multivariate analysis suggested that age, histology, historic stage and chemotherapy were independent prognostic factors for OS and primary site, surgery, historic stage and chemotherapy for CSS. The nomograms based on multivariate models were developed and validated for predicting 3- and 5-year OS and CSS, with a C-index of 0.686 and 0.707, respectively. In the external validation set, the C-index was 0.700 for OS and 0.722 for CSS. CONCLUSION: ICD-O-3 histology, historic stage and chemotherapy were independent prognostic factors for OS and primary site, surgery, historic stage and chemotherapy for CSS. The constructed nomograms could provide individual prediction for MPNST patients and assist oncologists in making accurate survival evaluation.

Outcome and prognostic factors in pediatric malignant peripheral nerve sheath tumors: An analysis of the European Pediatric Soft Tissue Sarcoma Group (EpSSG) NRSTS-2005 prospective study.

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNST) are rare tumors of childhood. The role of standard chemotherapy in unresectable MPNST is still unclear. We report the outcome and prognostic factors in the EpSSG risk-adapted prospective study for localized pediatric MPNST. METHODS: Patients were stratified into four treatment groups defined by surgical resection, tumor size, and tumor grade (G): (a) surgery-only group-resected tumors G1; (b) adjuvant radiotherapy group-R0/R1, G2 tumors; (c) adjuvant chemotherapy group-R0/R1, G3 tumors; and (d) neoadjuvant chemotherapy group-R2 resected tumors and/or nodal involvement. Chemotherapy consisted of four courses of ifosfamide-doxorubicin and two courses of ifosfamide concomitant with radiotherapy (50.4-54 Gy). RESULTS: Overall, the study included 51 patients. The 5-year event-free survival (EFS) and overall survival (OS) were 52.9% (95% confidence interval, 38.1-65.8) and 62.1% (46.7-74.3), respectively. The 5-year EFS was 92% (56.6-98.9) for treatment group 1 (N = 13), 33% (0.9-77.4) for treatment group 2 (N = 4), 29% (4.1-61.2) for treatment group 3 (N = 7), and 42% (23.1-60.1) for treatment group 4 (N = 27). Response rate to chemotherapy (partial response + complete response) in patients with measurable disease was 46%. The presence of neurofibromatosis type 1 (NF1; 51% of patients) was an independent poor prognostic factor for OS and EFS. CONCLUSION: The outcome for patients with resectable MPNST was excellent. Standard ifosfamide-doxorubicin for unresectable MPNST rendered the best reported outcome. Children with NF1 disease seem to have worse prognosis.

Inferior survival for patients with malignant peripheral nerve sheath tumors defined by aberrant TP53.

Malignant peripheral nerve sheath tumor is a rare and aggressive disease with poor treatment response, mainly affecting adolescents and young adults. Few molecular biomarkers are used in the management of this cancer type, and although TP53 is one of few recurrently mutated genes in malignant peripheral nerve sheath tumor, the mutation prevalence and the corresponding clinical value of the TP53 network remains unsettled. We present a multi-level molecular study focused on aberrations in the TP53 network in relation to patient outcome in a series of malignant peripheral nerve sheath tumors from 100 patients and 38 neurofibromas, including TP53 sequencing, high-resolution copy number analyses of TP53 and MDM2, and gene expression profiling. Point mutations in TP53 were accompanied by loss of heterozygosity, resulting in complete loss of protein function in 8.2% of the malignant peripheral nerve sheath tumors. Another 5.5% had MDM2 amplification. TP53 mutation and MDM2 amplification were mutually exclusive and patients with either type of aberration in their tumor had a worse prognosis, compared to those without (hazard ratio for 5-year disease-specific survival 3.5, 95% confidence interval 1.78-6.98). Both aberrations had similar consequences on the gene expression level, as analyzed by a TP53-associated gene signature, a property also shared with the copy number aberrations and/or loss of heterozygosity at the TP53 locus, suggesting a common "TP53-mutated phenotype" in as many as 60% of the tumors. This was a poor prognostic phenotype (hazard ratio = 4.1, confidence interval:1.7-9.8), thus revealing a TP53-non-aberrant patient subgroup with a favorable outcome. The frequency of the "TP53-mutated phenotype" warrants explorative studies of stratified treatment strategies in malignant peripheral nerve sheath tumor.

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.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

The clinical course and role of surgery in pediatric malignant peripheral nerve sheath tumors: a database study.

OBJECTIVE: Malignant peripheral nerve sheath tumors (MPNSTs) are rare tumors found throughout the body, with their clinical course in children still not completely understood. Correspondingly, this study aimed to determine survival outcomes and specific clinical predictors of survival in this population from a large national database. METHODS: All patients with MPNSTs aged ≤ 18 years in the US National Cancer Database (NCDB) between 2005 and 2016 were retrospectively reviewed. Data were summarized, and overall survival was modeled using Kaplan-Meier and Cox regression analyses. RESULTS: A total of 251 pediatric patients with MPNSTs (132 [53%] females and 119 [47%] males) were identified; the mean age at diagnosis was 13.1 years (range 1-18 years). There were 84 (33%) MPNSTs located in the extremities, 127 (51%) were smaller than 1 cm, and 22 (9%) had metastasis at the time of diagnosis. In terms of treatment, surgery was pursued in 187 patients (74%), chemotherapy in 116 patients (46%), and radiation therapy in 129 patients (61%). The 5-year overall survival rate was estimated at 52% (95% CI 45%-59%), with a median survival of 64 months (range 36-136 months). Multivariate regression revealed that older age (HR 1.10, p < 0.01), metastases at the time of diagnosis (HR 2.14, p = 0.01), and undergoing biopsy only (HR 2.98, p < 0.01) significantly and independently predicted a shorter overall survival. Chemotherapy and radiation therapy were not statistically significant. CONCLUSIONS: In this study, the authors found that older patient age, tumor metastases at the time of diagnosis, and undergoing only biopsy significantly and independently predicted poorer outcomes. Only approximately half of patients survived to 5 years. These results have shown a clear survival benefit in pursuing maximal safe resection in pediatric patients with MPNSTs. As such, judicious workup with meticulous resection by an expert team should be considered the standard of care for these tumors in children.

Characterization of PD-1/PD-L1 immune checkpoint expression in soft tissue sarcomas.

Inhibitors of the programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) immune checkpoint system are used for treating various malignancies. However, evidence on their use in soft tissue sarcomas (STS) is limited. This study aimed to retrospectively investigate the relationship between the expression of PD-1/PD-L1 and related antigens in STS, and their association with clinical characteristics. Immunostaining for CD4, CD8, PD-1, PD-L1, IL-2, and IFN-γ was performed using pathological specimens harvested at the time of biopsy from 10 patients with undifferentiated pleomorphic sarcoma (UPS), nine with myxofibrosarcoma (MFS), and three with malignant peripheral nerve sheath tumor (MPNST) who were treated at our hospital. Subsequently, the positive immunostaining cell rates were calculated. We also examined the correlation between each immune positive cell rate and age, tissue grade, size, and maximum standardized uptake (SUV-max) values. The 3-year event-free survival (EFS) and overall survival (OS) rates were compared between the positive and negative groups (positive rate >10%; negative <10%) for various immune stains. The positive rates were also compared between the presence and absence of events groups. There was positive staining for the immune checkpoint molecules in every STS type except for PD-1 in MPNST. CD4, CD8, and PD-1 stained lymphocytes in close proximity to the tumor in adjacent tissue sections. A positive correlation was observed between the positive cell rates of each immune component including inflammatory cytokines such as IL-2 and IFN-γ. Additionally, the clinical features positively correlated with the positive PD-1/PD-L1 expression rates. No significant differences in the 3-EFS and OS rates was observed between the PD-1/PD-L1 positive and negative groups. Our results suggest that an inducible immune checkpoint mechanism may be involved in UPS, MFS, and MPNST.

Clinicopathological and prognostic significance of H3K27 methylation status in malignant peripheral nerve sheath tumor: correlation with skeletal muscle differentiation.

Malignant peripheral nerve sheath tumor (MPNST) is a very aggressive peripheral nerve sheath-derived sarcoma, which is one of the most difficult tumors to diagnose due to its wide spectrum of histological findings and lack of specific immunohistochemical markers. Recently, it has been reported that losses of expression of H3K27me3 and H3K27me2 caused by PRC2 dysfunction may be useful diagnostic markers for MPNST, but there is no consensus on their clinicopathological significance. Here, we investigated the relationship between loss of H3K27 methylation and various parameters and clarified the clinicopathological significance of such loss. We analyzed the clinicopathological and immunohistochemical features in 84 MPNST cases. Complete losses of H3K27me3 and H3K27me2 were observed in 37 (44%) and 29 (35%) cases, respectively. Losses of H3K27me3 and H3K27me2 were significantly correlated with myogenic immunopositivity (H3K27me3 vs. desmin, P = 0.0051; H3K27me3 vs. myogenin, P = 0.0009; H3K27me2 vs. myogenin, P = 0.042). Meanwhile, there were significant correlations between preservation of immunohistochemical neurogenic markers and intact H3K27me3 and H3K27me2 (H3K27me3 vs. S-100 protein, P = 0.0019; H3K27me3 vs. SOX10, P = 0.014; H3K27me2 vs. S-100 protein, P = 0.0011; H3K27me2 vs. SOX10, P = 0.0087). In multivariate analysis, local recurrence, distant metastasis, high FNCLCC grade, and loss of SOX10 expression were independent prognostic factors for overall survival. H3K27me3 and H3K27me2 expression was retained in all 26 cases of rhabdomyosarcoma non-alveolar subtype. In conclusion, we suggest that H3K27me3 and H3K27me2 immunonegativity is useful but not definitive for diagnosing MPNST. Complete loss of H3K27 methylation may be involved in aggressive transdifferentiation from neural differentiation to skeletal muscle differentiation in MPNST.

Malignant Peripheral Nerve Sheath Tumors: A Single Institution's Experience Using Combined Surgery and Radiation Therapy.

PURPOSE: The purpose of this study is to investigate local control (LC), survival outcomes, and associated prognostic factors for patients with malignant peripheral nerve sheath tumors (MPNSTs) treated with combined surgery and radiation therapy (RT). METHODS: We reviewed the medical records of 71 consecutive patients treated with surgery and RT for localized MPNST between 1965 and 2012. Preoperative RT was used to treat 23 patients (32%) to a median dose of 50 Gy (range, 50 to 60 Gy), whereas 48 (68%) received postoperative RT to a median dose of 64 Gy (range, 45 to 70 Gy). RESULTS: Median follow-up for living patients was 118 months (range, 21 to 512 mo). The 5-year LC, distant metastatic free survival, and disease-specific survival rates were 84%, 62%, and 66%, respectively. To identify predictors of outcome, several multivariate models were constructed: (1) positive/uncertain surgical margin status was the only factor adversely associated local relapse at 5 years (28% vs. 5% for negative margins; P=0.02; hazard ratios 5.92; 95% confidence interval, 1.3-27.4). (2) No factors were significantly associated with distant metastatic free survival. Of the 35 patients (49%) who sustained disease relapse, only 3 were ultimately salvaged. Only 2 patients had grade 2 late toxicities (necrosis, fibrosis) based on Common Terminology Criteria for Adverse Events version 4.03 criteria, and 1 patient had grade 1 edema. CONCLUSIONS: Combination therapy with surgery and RT provides favorable LC. Distant recurrences, however, continue to be challenging with limited salvage success at the time of relapse.

The implications of intradural extension in paraspinal malignant peripheral nerve sheath tumors: effects on central nervous system metastases and overall survival.

OBJECTIVEIn this study, the authors sought to compare tumors with intradural extension to those remaining in the epidural or paraspinal space with the hypothesis that intradural extension may be a mechanism for seeding of the CSF with malignant cells, thereby resulting in higher rates of CNS metastases and shorter overall survival.METHODSThe authors searched the medical record for cases of malignant peripheral nerve sheath tumors (MPNSTs) identified from 1994 to 2017. The charts of the identified patients were then reviewed for tumor location to identify patients with paraspinal malignancy. All patients included in the study had tumor specimens that were reviewed in the surgical pathology department. Paraspinal tumors with intradural extension were identified in the lumbar, sacral, and spinal accessory nerves, and attempts were made to match this cohort to another cohort of patients who had paraspinal tumors of the cranial nerves and lumbar and sacral spinal regions without intradural extension. Further information was collected on all patients with and without intradural extension, including date of diagnosis by pathology specimen review; nerve or nerves of tumor origin; presence, location, and diagnostic date of any CNS metastases; and either the date of death or date of last follow-up.RESULTSThe authors identified 6 of 179 (3.4%) patients who had intradural tumor extension and compared these patients with 12 patients who harbored paraspinal tumors that did not have intradural extension. All tumors were diagnosed as high-grade MPNSTs according to the surgical pathology findings. Four of 6 (66.7%) patients with intradural extension had documented CNS metastases. The presence of CNS metastases was significantly higher in the intradural group than in the paraspinal group (intradural, 66.7% vs paraspinal, 0%; p < 0.01). Time from diagnosis until death was 11.2 months in the intradural group and approximately 72 months in the paraspinal, extradural cohort.CONCLUSIONSIn patients with intradural extension of paraspinal MPNSTs, significantly higher rates of CNS metastases are seen with a reduced interval of time from diagnosis to metastatic lesion detection. Intradural tumor extension is also a poor prognostic factor for survival, with these patients showing a reduced mean time from diagnosis to death.

Tumor maligno de las vainas nerviosas periféricas en la región maxilofacial: schwannoma maligno mandibular / Malignant tumor of peripheral nerve sheaths in the maxillofacial region: malignant mandibular schwannoma

Objetivo: Describir el diagnóstico y la resolución de un caso clínico de schwannoma maligno mandibular, una neopla- sia extremadamente rara en la región maxilofacial y con alto porcentaje de mortalidad. Caso clínico: Un paciente masculino de 56 años de edad acudió a la consulta por trismus, dolor y no cierre de la herida posextracción en maxilar inferior, con una evolución de tres meses. Se le solicitó una tomografía computada que evidenció lesión osteolítica y pieza dentaria retenida en la zona afectada. Se realizó la biopsia excisional. El diagnósti- co fue schwannoma maligno mandibular. Nueve meses des- pués del tratamiento quirúrgico y coadyuvante, el paciente falleció. Conclusiones: La derivación a un especialista y el análisis histopatológico tempranos permiten diagnosticar a tiempo este tipo de neoplasias. El schwannoma maligno es una enfermedad agresiva, con una tasa de supervivencia baja, pero la intervención oportuna y el diagnóstico precoz mejoran el pronóstico y la sobrevida del paciente (AU)

Aim: Describe the diagnosis and resolution of a clini- cal case of malignant mandibular schwannoma. An extremely rare neoplasm in the maxillary facial region, and with a high percentage of mortality. Clinical case: A 56-year-old male patient attended the consultation due to trismus, pain and non-closure of the post-extraction wound in the lower jaw, with an evolution of three months. He was asked for a computed tomography scan, that showed an osteolytic lesion and retained tooth in the af- fected area. Excisional biopsy is performed. The diagnosis was malignant mandibular schwannoma. After surgical and adjuvant treatment, the patient dies nine months later. Conclusion: Early referral to a specialist and histo- pathological analysis will allow to diagnose this type of neoplasms early. Malignant schwannoma is recorded as an aggressive disease with a low survival rate, but timely inter- vention and early diagnosis improves the prognosis and pa- tient survival (AU)

Neurogenic sarcomas: experience at the University of Toronto.

OBJECTIVE: Elucidation of the natural history and optimal management of neurogenic sarcomas is not straightforward, because of diagnostic difficulties and the low incidence of this disease. The majority of neurogenic sarcomas are categorized and treated as soft tissue sarcomas, and only a few centers have sufficient experience to add to our understanding of these malignant tumors. This article proposes an algorithm for the management of these tumors. METHODS: A cohort of 18 cases of neurogenic sarcoma (overall mean follow-up period after oncological diagnosis, 33.7 mo), representing approximately 3% of all soft tissue sarcomas treated at the University of Toronto Musculoskeletal Oncology Unit (Toronto, Canada) between 1989 and 1995, were reviewed. The clinical and pathological criteria used to establish the diagnosis of neurogenic sarcoma, the presenting symptoms, the tumor size and grade, the ability to obtain tumor-free margins during en bloc resection, the time to recurrence, and the overall survival rates were noted. A centralized pathological review of the biopsy was undertaken in all cases. RESULTS: A metastatic survey demonstrated localized disease for 16 of the 18 patients. The overall management strategy for these 16 neurogenic sarcomas with localized disease was to obtain local control by en bloc resection. Tumor size, tumor grade, and, most importantly, the ability to obtain tumor-free margins were all relevant prognostic factors for survival. Tumor-free surgical margins were obtained for 11 of 16 patients, with 9 of these 11 patients remaining disease-free. In contrast, all patients for whom tumor-free margins could not ultimately be achieved died as a result of their disease. CONCLUSION: Based on our experience, we propose an algorithm for the management of these rare tumors, for both optimal patient care and oncological research.

Intraspinal tumours in children--clinical presentation.

Intraspinal tumours in children are rare, the estimated average ratio of spinal to intracranial tumour in the paediatric population is 1:10. We reviewed our experience of paediatric spinal tumours over the period 1992-96. Nineteen patients presented during this time, 12 males and 7 females with the mean age of 7.8 years. The main presenting symptoms were pain, limb weakness, ataxia, sensory disturbance and spinal curvature abnormalities with a mean duration of 10 months. There was a wide variety of tumour types. All underwent a laminectomy with 8 having total tumour excision, 5 partial excision, and 6 had biopsies only. Five patients had extradural lesions and fourteen were intra-dural, four of which were extramedullary and six were intramedullary tumours. There were no major complications of surgery and only one patient had a CSF leak which was repaired. The average hospital stay was 15 days. Seven patients underwent radiotherapy and four had chemotherapy. Four patients are disease free and seven are symptom free after a mean follow-up of 2 years. Four patients died in this series with extensive diffuse tumours.

Ganglioneuroma mediastínico posterior / Posterior mediastinal ganglioneuroma

No disponible

Salvage surgical resection after high-dose ifosfamide (HDIF) based regimens in advanced soft tissue sarcoma (ASTS): a potential positive selection bias--a study of the Spanish group for research on sarcomas (GEIS).

PURPOSE: To assess the impact of different factors on response rate (RR), time to tumor progression (TTP), and overall survival time (OS) in patients with locally advanced or metastatic soft tissue sarcoma (ASTS), included in three protocols with high-dose ifosfamide (HDIF). PATIENTS AND METHODS: One hundred fifty six ASTS patients included in three consecutive phase II trials with HDIF (>10 g/m(2)), alone or in combination with doxorubicin (DX), were analyzed. Cofactors were institution, trial, gender, age, performance status, histologic type, grade of malignancy, prior radiotherapy, presence of locoregional disease, metastatic site, salvage surgery, number of organs involved, and disease-free interval. RESULTS: By multivariate analysis performance status >0 and lack of salvage surgery correlated with a poorer survival. A good-risk and a poor-risk group were identified, with median survival time (OS) of 29, 5, and 10 months, respectively (P = 0.00001). The 1-, 2-, and 3-year OS for 83 good-risk patients (either with PS = 0 or receiving salvage surgery) was 83, 44, and 29%, respectively, those figures being 37, 7, and 3% for 73 poor-risk patients. CONCLUSION: The design of randomized trials in ASTS including HDIF should consider those prognostic factors as stratification variables.