Prognostic factors of alveolar soft part sarcoma in children and adolescents: A population-based study.

PURPOSE: Alveolar Soft Part Sarcoma (ASPS) is an exceedingly rare and aggressive cancer in children. Our objective was to conduct a population-based cohort study to forecast overall survival (OS) in pediatric ASPS patients. METHODS: We utilized the Surveillance, Epidemiology, and End Results (SEER) database to identify all pediatric ASPS patients diagnosed between 1975 and 2019. Kaplan-Meier estimations were employed to construct survival curves based on various criteria. Survival curves were compared using the log-rank test. Cox proportional-hazards regression was utilized to determine variables associated with OS. Additionally, we constructed a nomogram to predict overall survival in pediatric ASPS patients. RESULTS: A total of 103 pediatric ASPS patients were identified. Predominantly, the tumors affected females (62.2 %), and most of them located in the extremities (53.4 %). The majority of patients underwent surgery (83.5 %). Survival rates declined with increasing tumor size, and patients with localized tumors exhibited significantly better prognoses than those with distant tumors. Surgery conferred superior survival outcomes compared to no surgery. Cox proportional hazard regression analysis identified SEER stage and surgery as important independent predictors of survival. CONCLUSIONS: Our study highlights SEER stage and surgery as key predictors of OS in pediatric ASPS, offering crucial epidemiological insights for clinical management.

Characterization of alveolar soft part sarcoma using a large national database.

BACKGROUND: Alveolar soft part sarcoma is a rare, histologic subtype of soft tissue sarcoma that remains poorly defined. We aimed to describe patient characteristics and treatment patterns and to examine factors associated with survival for patients with alveolar soft part sarcoma. METHODS: After identifying patients with alveolar soft part sarcoma in the National Cancer Database, we recorded their clinicopathologic characteristics. Univariable log-rank survival analysis and Cox proportional hazards model were employed. For context, survival comparisons were included for patients with other sarcoma subtypes. RESULTS: Overall, 293 patients with alveolar soft part sarcoma were identified. Interestingly, patients with head and neck tumors were least likely to present with distant disease (40%, P = .025). The majority of patients underwent resection (n = 183, 63%). Among those, no predictors of lesser survival were identified other than the presence of metastases (hazard ratio 6.04, P ≤ .001). Patients with stage IV alveolar soft part sarcoma who underwent resections experienced improved survival relative to similar patients with more common subtypes of soft tissue sarcomas (P ≤ .001). CONCLUSION: Alveolar soft part sarcoma is exceedingly rare, and patients often present with metastases. Primary tumors can occur anywhere in the body, and location impacts the rates of metastases at presentation. Resection is associated with a favorable survival advantage when compared to other, more common histologic subtypes of soft tissue sarcomas.

Diagnosis, Prognosis, and Treatment of Alveolar Soft-Part Sarcoma: A Review.

Importance: Alveolar soft-part sarcoma (ASPS) is a rare, translocation-driven sarcoma of the soft tissues. Alveolar soft-part sarcoma often affects young adults and is characterized by indolent behavior but early evidence of metastatic spread. After recognition of ASPS as a specific entity in 1952, retrospective data indicated prolonged survival in patients with metastases, despite inherent resistance to conventional doxorubicin-based chemotherapy. Tyrosine kinase inhibitors and immune checkpoint inhibitors have provided unexpected new treatment strategies for ASPS. Observations: This review includes articles published between 1952 and March 1, 2018. With the introduction of new molecular diagnostic tools and therapies, the distinctive features of ASPS have become more evident. The identification and better understanding of molecular pathways activated by the characteristic t(X;17)(p11;q25) translocation and its correspondent chimeric ASPSCR1-transcription factor E3 (TFE3) fusion protein open new paths to drug development. The associations of TFE3 and facilitation of an immunosuppressive microenvironment provide a rationale for exploring treatments that affect the balance between T-effector cells and T-regulatory cells. Tyrosine kinase inhibitors, such as sunitinib, cediranib, and pazopanib, show activity with either tumor responses or disease stabilization in more than 50% of the cases. Given the association of new agents with patient outcomes, it is too early to say whether metastatic ASPS should still be considered incurable in all patients. Conclusions and Relevance: The biologic outcomes of the canonical genomic event in ASPS remain under investigation; a better understanding of the tumor microenvironment and the multiple pathways activated in this sarcoma, including unusual bioenergetics, MET signaling, and angiogenesis, should lead to more rational therapy. Basket trials and related prospective studies focusing on the intersection of specific signaling pathways and diseases with unique genomic features, such as ASPS, will provide an understanding of new options for care.

Alveolar soft-part sarcoma: Primary metastatic disease and metastatic relapse occurring during long-term follow-up: Treatment results of four Cooperative Weichteilsarkom Studiengruppe (CWS) trials and one registry.

BACKGROUND: Patients with metastatic alveolar soft-part sarcoma (ASPS) are known to have a very poor prognosis. Little is known about best treatment of primary metastatic disease (MD) or relapsed metastatic disease (rMD). PATIENTS AND METHODS: Patients with localized disease (LD), primary MD, and metastatic recurrence after complete remission (CR) treated within the CWS-86, -91, -96, -2002P trials and the recent registry SoTiSaR (1985-2016) were analyzed. RESULTS: Fifteen of 61 patients had primary metastases at initial diagnosis at the age of 14.6 years (range, 7.8-19.7). Nine of 46 patients with initial LD suffered of rMD at a median age of 9.9 years (range, 3.5-30), 3.75 years (0.75-21) after CR of primary disease. Complete resection (microscopically or macroscopically) was possible in 2 of 15 patients with MD and in 5 of 9 with rMD. RT was administered in 4 of 15 MD and 1 of 9 rMD. Chemotherapy was administered to 11 of 15 MD and 3 of 9 rMD, targeted therapy to 3 of 15 MD and 1 of 9 rMD. Median time to progression of patients treated with targeted therapy (n = 4), CHT (n = 14), and resection only (n = 6) was 56, 17, and 23 months, respectively. The 5-year event-free survival and overall survival (OS) rates were 19.8% and 61%, respectively, for patients with MD compared with 79% and 98% for patients with LD. The 5-year progression-free survival and OS were 67% and 100% for patients with rMD. CONCLUSIONS: Complete tumor resection correlates with long-term survival in patients with primary and relapsed MD.

Alveolar soft part sarcoma: Clinical presentation, treatment, and outcome in a series of 13 patients.

BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare soft tissue tumor that typically affects young patients. Similar to other soft tissue sarcomas, it has high pulmonary metastasis ability, whereas compared with other soft tissue sarcomas, it has high brain metastasis ability. Because of the rarity of the disease, most studies on ASPS have been case reports and small series studies. METHOD: We performed a retrospective study to evaluate the clinical and pathological features and oncological results in a consecutive series of patients with localized or metastatic ASPS treated at our institute between 1994 and 2014. Demographics, location, severity of disease, treatment provided, progression-free survival, and overall survival were evaluated. RESULTS: A total of 13 patients were investigated. The most common locations of primary tumor were the thigh (n = 6, 47%), followed by the flank (n = 3, 23%), forearm (n = 2, 15%), and calf (n = 2, 15%). Three patients were initially diagnosed as having hemangiomas elsewhere. These patients received unplanned intralesional excision. All the patients received wide tumor resection at our institute. Over the average follow-up period of 80.5 months (range: 36-133 months), the 5-year overall survival rate was 67.5%. Four patients were continuously disease free (31%), six were living with disease (46%), and three died of disease (23%). Of nine patients who presented with distant pulmonary metastasis, two had bony and brain metastases. The 5-year survival rate was 66.7% in patients who received chemotherapy and those who did not (p = 0.941). CONCLUSION: The treatment strategy for ASPS is wide resection, and postoperative chemotherapy may be crucial for long-term survival. In addition, this type of tumor has a high distant metastasis rate at the time of diagnosis, particularly in the lungs and brain.

Alveolar soft part sarcoma in children and young adults: A report of 69 cases.

BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare mesenchymal tumor characterized by ASPL-TFE3 translocation. Apart from complete surgical resection, there is no standard management strategy. PROCEDURE: The clinical data of 69 children and young adults less than 30 years old with ASPS diagnosed from 1980-2014 were retrospectively collected from four major institutions. RESULTS: Median age at diagnosis was 17 years (range: 1.5-30). Forty-four (64%) were female. Median follow-up was 46 months (range: 1-409). Most common primary sites were limbs (58%) and trunk (24%). ASPL-TFE3 translocation was present in all 26 patients tested. IRS postsurgical staging was I in 19 (28%), II in 7 (10%), III in 5 (7%), and IV in 38 (55%) patients. The 5-year event-free survival (EFS) and overall survival (OS) were 38% and 72%, respectively. The 5-year EFS and OS were 80% and 87%, respectively, for the 31 patients with localized tumors (IRS-I-II-III), and 7% and 61%, respectively, for the 38 patients with metastatic tumors (IRS-IV). Of 11 IRS-IV patients who received targeted therapy upfront, two had partial response, six had stable disease, and three had progressive disease. Median time to progression for IRS-IV patients was 12 months for those treated with targeted therapy, 7 months for cytotoxic chemotherapy (N = 15), and 4 months for observation only (N = 6). CONCLUSION: Localized ASPS has a good prognosis after gross total resection. ASPS is resistant to cytotoxic chemotherapy. Although there are no curative therapies for patients with metastatic disease, prolonged disease stabilization may be achieved with targeted therapies.

Activity and safety of crizotinib in patients with alveolar soft part sarcoma with rearrangement of TFE3: European Organization for Research and Treatment of Cancer (EORTC) phase II trial 90101 'CREATE'.

Background: Alveolar soft part sarcoma (ASPS) is an orphan malignancy associated with a rearrangement of transcription factor E3 (TFE3), leading to abnormal MET gene expression. We prospectively assessed the efficacy and safety of the MET tyrosine kinase inhibitor crizotinib in patients with advanced or metastatic ASPS. Patients and methods: Eligible patients with reference pathology-confirmed ASPS received oral crizotinib 250 mg bd. By assessing the presence or absence of a TFE3 rearrangement, patients were attributed to MET+ and MET- sub-cohorts. The primary end point was the objective response rate (ORR) according to local investigator. Secondary end points included duration of response, disease control rate (DCR), progression-free survival (PFS), progression-free rate, overall survival (OS) and safety. Results: Among 53 consenting patients, all had a centrally confirmed ASPS and 48 were treated. A total of 45 were eligible, treated and assessable. Among 40 MET+ patients, 1 achieved a confirmed partial response (PR) that lasted 215 days and 35 had stable disease (SD) as best response (ORR: 2.5%, 95% CI 0.6% to 80.6%). Further efficacy end points in MET+ cases were DCR: 90.0% (95% CI 76.3% to 97.2%), 1-year PFS rate: 37.5% (95% CI 22.9% to 52.1%) and 1-year OS rate: 97.4% (95% CI 82.8% to 99.6%). Among 4 MET- patients, 1 achieved a PR that lasted 801 days and 3 had SD (ORR: 25.0%, 95% CI 0.6% to 80.6%) for a DCR of 100% (95% CI 39.8% to 100.0%). The 1-year PFS rate in MET- cases was 50% (95% CI 5.8% to 84.5%) and the 1-year OS rate was 75% (95% CI 12.8% to 96.1%). One patient with unknown MET status due to technical failure achieved SD but stopped treatment due to progression after 17 cycles. The most common crizotinib-related adverse events were nausea [34/48 (70.8%)], vomiting [22/48 (45.8%)], blurred vision [22/48 (45.8%)], diarrhoea (20/48 (41.7%)] and fatigue [19/48 (39.6%)]. Conclusion: According to European Organization for Research and Treatment of Cancer (EORTC) efficacy criteria for soft tissue sarcoma, our study demonstrated that crizotinib has activity in TFE3 rearranged ASPS MET+ patients. Clinical trial number: EORTC 90101, NCT01524926.

Alveolar soft part sarcoma in children and adolescents: The European Paediatric Soft Tissue Sarcoma study group prospective trial (EpSSG NRSTS 2005).

BACKGROUND: As alveolar soft part sarcomas (ASPS) are rare with no prospective series within pediatric sarcoma trials, the European Paediatric Soft Tissue Sarcoma Study Group (EpSSG) examined the clinical data and outcomes of ASPS enrolled in a multinational study of nonrhabdomyosarcoma soft tissue sarcomas (NRSTS). PATIENTS AND METHODS: Twenty-two patients with ASPS were enrolled into the EpSSG NRSTS 2005 study. After surgical resection, subsequent treatment depended on the stratification of patients for completeness of resection and Intergroup Rhabdomyosarcoma Study (IRS) stage, size, and French Federation of Cancer Centres Sarcoma Group (FNCLCC) grade. Chemotherapy using ifosfamide and doxorubicin was performed in IRS group III. Radiotherapy was performed in IRS groups II and III, and FNCLCC grades 2 and 3 tumors. RESULTS: The median age at diagnosis was 11.5 years (range 2.7-17.5 years). The majority in the series had localized disease (20), with small IRS I tumors (12), and in total 19 had surgical resection upfront. Of the four patients who received conventional chemotherapy, there were no responses. Three of 20 patients with localized tumors and all metastatic patients developed metastases. The median follow up of patients with localized disease is 61.7 months (range 25.7-135.5 months) from diagnosis. The 5-year event-free survival is 94.7% (95% confidence interval: 68.1-99.2), and therefore the overall survival (OS) is 100%. CONCLUSION: This report demonstrates the ability to run prospective pediatric studies in NRSTS in multiple European countries, despite the small numbers of ASPS patients. We can conclude that for the majority with small resected tumors, there were few events and no deaths.

Phase 2 study of dasatinib in patients with alveolar soft part sarcoma, chondrosarcoma, chordoma, epithelioid sarcoma, or solitary fibrous tumor.

BACKGROUND: Alveolar soft part sarcoma (ASPS), chondrosarcoma (CS), chordoma, epithelioid sarcoma, and solitary fibrous tumor (SFT) are malignant tumors that are relatively resistant to chemotherapy and for which more effective drug therapy is needed. METHODS: The 5 listed subtypes were enrolled into a single indolent sarcoma cohort in a phase 2 study of dasatinib using a Bayesian continuous monitoring rule for enrollment. The primary objective was to estimate the 6-month progression-free survival (PFS) rate according to the Choi criteria with a target of ≥50%. Cross-sectional imaging was performed before the start of treatment, every 2 months for 6 months, and then every 3 months during treatment. The 2- and 5-year survival rates were determined. RESULTS: One hundred sixteen patients were enrolled within 45 months, and 109 began treatment with dasatinib. The 6-month PFS rate and the median PFS were 48% and 5.8 months, respectively. The PFS rate at 6 months was highest with ASPS (62%) and lowest with SFT (30%). More than 10% of the patients with ASPS, CS, or chordoma had stable disease for more than 1 year. Collectively, for all 5 subtypes, the 2- and 5-year overall survival rates were 44% and 13%, respectively. An objective response was observed in 18% of the patients with CS or chordoma. CONCLUSIONS: Dasatinib failed to achieve control of sarcoma growth for at least 6 months in more than 50% of the patients in this trial according to the Choi tumor response criteria. An objective tumor response and prolonged stable disease was observed in >10% of patients with CS or chordoma. Cancer 2017;90-97. © 2016 American Cancer Society.

Prognostic factors in alveolar soft part sarcoma: A SEER analysis.

OBJECTIVES: We reviewed the clinical characteristics and outcomes of patients treated for alveolar soft part sarcoma (ASPS) and analyzed the effect of surgery for patients presenting with and without metastatic disease (DM). METHODS: The SEER Registry was queried for patients with ASPS from 1973-2012. The Kaplan-Meier estimate and Cox proportional hazards were used to analyze survival outcomes and risk variables. RESULTS: Among 251 patients, 43% had DM and 67% locoregional disease (LR) on presentation. The 5-year overall survival (OS) for all patients was 56% (82% and 27% for LR and DM, respectively). Multivariate analysis identified older age (hazard ratio [HR] = 1.03 per year, P < 0.001), tumor size >10 cm (HR = 2.76, P = 0.013), DM at diagnosis (HR = 3.79, P < 0.001), and truncal primary site (HR = 1.63, P = 0.035) as independent factors predicting worse OS. For LR patients, surgery plus radiotherapy (RT) resulted in better OS compared to surgery alone P = 0.014. For DM patients, primary site surgery significantly improved survival (P < 0.001). CONCLUSION: ASPS presents with high metastasis rate but has a relatively indolent clinical course and a favorable prognosis with prolonged survival. Aggressive treatment using adjuvant RT with surgery is indicated in patients with LR disease and surgery is indicated in patients presenting with DM. J. Surg. Oncol. 2016;113:581-586. © 2016 Wiley Periodicals, Inc.

[Alveolar soft part sarcoma in pediatric patients]. / Le sarcome alvéolaire des parties molles de l'enfant et l'adolescent.

Alveolar soft part sarcoma, ASPS, is a rare malignant tumor, with preferential primary localization in limbs, usually occurring in adolescents and young adults. This sarcoma, well defined histologically and at molecular level, has an indolent course, but a high potential metastatic pulmonary and cerebral evolution, sometimes late. ASPS is characterized by an almost specific translocation t(X, 17)(p11;25) which creates a fusion protein, APSL-TFE3, acting as an aberrant transcription factor. An in-bloc resection of the primary tumor is the treatment of choice in cases of localized disease. Conventional chemotherapy is generally ineffective. The role of radiotherapy is discussed in case of micro- or macroscopical incomplete residue. It seems to reduce local recurrence, but did not influence overall survival. The 5 years survival rate in children, adolescents and young adults is close to 80% in case of localized disease but poorer in presence of metastases. Recently, systemic anti-tumoral treatments have been focused on the use of targeted therapies. Anti-angiogenic drugs and tyrosine kinase inhibitors are the most promising approaches, but require further study. Prognostic risk factors in the literature are age (>10Y), tumor size (>5cm) and presence of metastases. This article reviews the clinical manifestations, diagnosis modalities, radiographic characteristics and therapeutic strategy of this disease in the pediatric population.

Anticipated intraoperative electron beam boost, external beam radiation therapy, and limb-sparing surgical resection for patients with pediatric soft-tissue sarcomas of the extremity: a multicentric pooled analysis of long-term outcomes.

PURPOSE: To perform a joint analysis of data from 3 contributing centers within the intraoperative electron-beam radiation therapy (IOERT)-Spanish program, to determine the potential of IOERT as an anticipated boost before external beam radiation therapy in the multidisciplinary treatment of pediatric extremity soft-tissue sarcomas. METHODS AND MATERIALS: From June 1993 to May 2013, 62 patients (aged <21 years) with a histologic diagnosis of primary extremity soft-tissue sarcoma with absence of distant metastases, undergoing limb-sparing grossly resected surgery, external beam radiation therapy (median dose 40 Gy) and IOERT (median dose 10 Gy) were considered eligible for this analysis. RESULTS: After a median follow-up of 66 months (range, 4-235 months), 10-year local control, disease-free survival, and overall survival was 85%, 76%, and 81%, respectively. In multivariate analysis after adjustment for other covariates, tumor size >5 cm (P=.04) and R1 margin status (P=.04) remained significantly associated with local relapse. In regard to overall survival only margin status (P=.04) retained association on multivariate analysis. Ten patients (16%) reported severe chronic toxicity events (all grade 3). CONCLUSIONS: An anticipated IOERT boost allowed for external beam radiation therapy dose reduction, with high local control and acceptably low toxicity rates. The combined radiosurgical approach needs to be tested in a prospective trial to confirm these results.

High-resolution array CGH and gene expression profiling of alveolar soft part sarcoma.

PURPOSE: Alveolar soft part sarcoma (ASPS) is a soft tissue sarcoma with poor prognosis, and little molecular evidence exists for its origin, initiation, and progression. The aim of this study was to elucidate candidate molecular pathways involved in tumor pathogenesis. EXPERIMENTAL DESIGN: We employed high-throughput array comparative genomic hybridization (aCGH) and cDNA-Mediated Annealing, Selection, Ligation, and Extension Assay to profile the genomic and expression signatures of primary and metastatic ASPS from 17 tumors derived from 11 patients. We used an integrative bioinformatics approach to elucidate the molecular pathways associated with ASPS progression. FISH was performed to validate the presence of the t(X;17)(p11.2;q25) ASPL-TFE3 fusion and, hence, confirm the aCGH observations. RESULTS: FISH analysis identified the ASPL-TFE3 fusion in all cases. aCGH revealed a higher number of numerical aberrations in metastatic tumors relative to primaries, but failed to identify consistent alterations in either group. Gene expression analysis highlighted 1,063 genes that were differentially expressed between the two groups. Gene set enrichment analysis identified 16 enriched gene sets (P < 0.1) associated with differentially expressed genes. Notable among these were several stem cell gene expression signatures and pathways related to differentiation. In particular, the paired box transcription factor PAX6 was upregulated in the primary tumors, along with several genes whose mouse orthologs have previously been implicated in Pax6 DNA binding during neural stem cell differentiation. CONCLUSION: In addition to suggesting a tentative neural line of differentiation for ASPS, these results implicate transcriptional deregulation from fusion genes in the pathogenesis of ASPS.

Histological analysis suggests an invasion-independent metastatic mechanism in alveolar soft part sarcoma.

Alveolar soft part sarcoma (ASPS) is a rare soft tissue tumor characterized by pseudoalveolar growths associated with abundant sinusoidal vessels. It has a high proclivity to blood-borne metastasis, but the exact mechanism of spread has not been widely discussed, and detailed histological analysis of vascular involvement is still lacking. In this study, we histologically analyzed 32 surgically resected ASPSs, with particular attention to the mode of vascular involvement. Among 188 instances of unequivocal vascular involvement, 184 (98%) were in the form of variously sized cohesive clusters that were completely enveloped by endothelial cells, confirmed by CD31 immunostaining. Discohesive intravascular tumor cells without endothelial wrapping were rare (2%). The clinical relevance of vascular involvement was supported by survival analysis where the average number of vascular involvements per slide was an independent risk factor for shorter progression-free survival. Our findings suggest that ASPSs do not actively break through the vascular walls to initiate the metastatic process. They instead suggest that ASPSs almost exclusively follow the recently postulated "invasion-independent mechanism" for entry into circulation, in which cancer cells are shed into vessels, while being completely enveloped by endothelial cells, and are subsequently entrapped at recipient organs. Because the latter mechanism is reportedly dependent on tumor angiogenesis and vascular remodeling, our data provide a morphological rationale for the use of anti-angiogenic therapy to treat ASPSs.

Paediatric and adolescent alveolar soft part sarcoma: A joint series from European cooperative groups.

BACKGROUND: Alveolar soft part sarcomas (ASPS) are generally chemo- and radio-resistant mesenchymal tumours, with no standardized treatment guidelines. We describe the clinical behaviour of paediatric ASPS and compare these features to previously reported adult series. PATIENTS AND METHODS: The clinical data of 51 children and adolescents with ASPS, prospectively enrolled in or treated according to seven European Paediatric trials were analysed. RESULTS: Median age was 13 years [range: 2-21]. Primary sites included mostly limbs (63%). IRS post-surgical staging was: IRS-I (complete resection) 35%, II (microscopic residual disease) 20%, III (gross residual disease) 18% and IV (metastases) 27%. Only 3 of the 18 evaluable patients (17%) obtained a response to conventional chemotherapy. After a median follow-up of 126 months (range: 9-240), 14/18 patients with IRS-I tumour, 10/10 IRS-II, 7/9 IRS-III and 2/14 IRS-IV were alive in remission. Sunitinib treatment achieved two very good partial responses in four patients. Ten-year overall survival (OS) and event free survival (EFS) was 78.0 ± 7% and 62.8 ± 7% respectively. Stage IV, size >5 cm and T2 tumours had a poorer outcome, but only IRS staging was an independent prognostic factor. CONCLUSIONS: ASPS is a very rare tumour frequently arising in adolescents and in the extremities, and chemo resistant. Local surgical control is critical. ASPS is a poorly chemo sensitive tumour. For IRS-III/IV tumours, delayed radical local therapies including surgery are essential. Metastatic patients had a poor prognosis but targeted therapies showed promising results.

Alveolar soft part sarcoma 'revisited': clinicopathological review of 47 cases from a tertiary cancer referral centre, including immunohistochemical expression of TFE3 in 22 cases and 21 other tumours.

BACKGROUND: Alveolar soft part sarcoma accounts for 0.5-1.0% of soft tissue sarcomas in the United States. At our Hospital, it constitutes 1.8% of the newly diagnosed soft tissue sarcomas. Lately, TFE3 has been found to be a useful immunohistochemical marker for diagnosing this sarcoma. METHODS: We reviewed 47 cases of alveolar soft part sarcoma that were either treated at Tata Memorial Hospital, Mumbai, India, or were referred in consultation from various parts of India. TFE3 immunohistochemical staining was performed on 22 alveolar soft part sarcomas and on 21 other tumours. RESULTS: Unlike most other large series, 58% of patients were males and 40% were females. The ages ranged from 2 to 54 years (median 24 years). Tumours were located in the deep soft tissues of lower extremities (54%), upper extremities (13%), head and neck (11%), retroperitoneum (10%), chest wall (6%), pelvis (4%), and were positive for TFE3 (20/22, 91%), desmin (3/18, 16%), myoglobin (1/6, 17%) and smooth muscle actin (1/9, 11%). TFE3 was positive in tumour controls that comprised paragangliomas (3/4), translocation related renal cell carcinoma (1/1), adrenocortical carcinoma (1/3) and granular cell tumour (1/3). Treatment consisted of primary surgical excision, metastatectomy, chemotherapy and radiotherapy. Seven tumours (24%) recurred locally and 21 of 29 (72%) metastasised, mainly to the lungs. Follow-up information (5-108 months, median 27.5 months) was available for 22 patients. No patients died in the relatively short follow-up period. CONCLUSIONS: TFE3 is a useful immunohistochemical marker for diagnosis of an alveolar soft part sarcoma. Awareness of other tumours expressing TFE3 is vital. Alveolar soft part sarcoma has a high metastasis rate but relatively good short-term survival. Surgical excision with follow-up forms the present management.

Supracricoid laryngectomy with cricohyoidoepiglotto-pexy or cricohyoido-pexy: experience on 32 patients.

OBJECTIVE: Supracricoid laryngectomy (SCL) with Cricohyoidoepiglotto-pexy (CHEP) or Cricohyoido-pexy (CHP) is an organ preservation surgery indicated for early and selected advanced laryngeal cancers. To verify the clinical usefulness of supracricoid laryngectomy versus total laryngectomy, a retrospective review was conducted. METHODS: We summarized the clinical and postoperative data of 32 patients who received SCL over the past 9 years (1997-2005). Five-year survival rate of the SCL patient group (29 cases) was compared with that of the patient group receiving total laryngectomy (35 cases) within the same period. RESULTS: Wound infection was detected in 12 patients (38%). Those with severe infection, which required surgical intervention, included two cases of ruptured pexis and two cases showing cricoid cartilage necrosis induced by Forestier disease. There were two T4 cases that resulted in extensive excision. In one case, excision involved the posterior part of the cricoid cartilage resulting in insufficient closure of the neoglottis; the patient received total laryngectomy 30 months after SCL-CHEP because of persistent aspiration of liquid diet. In the other T4 case, the tumor invaded the thyroid and arytenoid cartilages but not the cricoid cartilage. Reposition of the remaining corniculate cartilage resulted in sufficient closure of the neoglottis; this patient subsequently acquired satisfactory laryngeal function. The 5-year overall survival rate was 86% for SCL group and 61% for the total laryngectomy group (limited to Stages III and IV glottic cancers). The causes of the four deaths were distant metastasis, neck metastasis, and intercurrent disease, respectively. Two patients are alive with distant disease. CONCLUSION: Through our experience in this series, the functional and oncological results of SCL showed certain advantages over those of total laryngectomy. Particularly, the clinical impact of SCL-CHEP was impressive; this technique needs is recommended to both head and neck surgeons and patients.

Angiogenesis-promoting gene patterns in alveolar soft part sarcoma.

PURPOSE: We examined a cohort of patients with alveolar soft part sarcoma (ASPS) treated at our institution and showed the characteristic ASPSCR1-TFE3 fusion transcript in their tumors. Investigation of potential angiogenesis-modulating molecular determinants provided mechanistic and potentially therapeutically relevant insight into the enhanced vascularity characteristic of this unusual tumor. EXPERIMENTAL DESIGN: Medical records of 71 patients with ASPS presenting at the University of Texas M.D. Anderson Cancer Center (1986-2005) were reviewed to isolate 33 patients with formalin-fixed paraffin-embedded material available for study. RNA extracted from available fresh-frozen and formalin-fixed paraffin-embedded human ASPS tumors were analyzed for ASPSCR1-TFE3 fusion transcript expression using reverse transcription-PCR and by angiogenesis oligomicroarrays with immunohistochemical confirmation. RESULTS: Similar to previous studies, actuarial 5- and 10-year survival rates were 74% and 51%, respectively, despite frequent metastasis. ASPSCR1-TFE3 fusion transcripts were identified in 16 of 18 ASPS samples. In the three frozen samples subjected to an angiogenesis oligoarray, 18 angiogenesis-related genes were up-regulated in tumor over adjacent normal tissue. Immunohistochemistry for jag-1, midkine, and angiogenin in 33 human ASPS samples confirmed these results. Comparison with other sarcomas indicates that the ASPS angiogenic signature is unique. CONCLUSION: ASPS is a highly vascular and metastatic tumor with a surprisingly favorable outcome; therapeutically resistant metastases drive mortality. Future molecular therapies targeting overexpressed angiogenesis-promoting proteins (such as those identified here) could benefit patients with ASPS.

Alveolar soft part sarcoma: a rare and enigmatic entity.

UNLABELLED: Alveolar soft part sarcoma is a rare malignant tumor with unusual clinical behavior. Treatment of alveolar soft part sarcoma has been difficult to evaluate because of the small numbers of cases seen, but it seemed that although treatment of the primary tumor in alveolar soft part sarcoma often is successful, treatment of metastatic tumors is unsuccessful. A review of outcome after treatment of primary and metastatic disease in the 15 patients in our database with alveolar soft part sarcoma was done in order to evaluate this issue. Nine of 15 patients presented with metastatic disease and one further patient developed metastases. Treatment of primary tumors involved surgical excision in all but one patient and radiation in all patients. Adjuvant chemotherapy was administered to one patient with localized disease and to six patients with metastatic disease. There were no local recurrences. Treatment of metastatic tumors involved chemotherapy in seven patients, metastectomy in three patients, and radiation in two patients. All instances of the metastatic disease either recurred or progressed. Overall survival was 75% at 5 years and 40% at 10 years with a mean survival of 6.5 years, despite the high number of patients with metastatic disease. Current treatment results in good local control of primary tumors, but poor control of metastatic tumors. New approaches to treatment of metastatic alveolar soft part sarcoma must be investigated and applied. LEVEL OF EVIDENCE: Therapeutic study, Level IV-1 (case series). See the Guidelines for Authors for a complete description of levels of evidence.