An open-label,phase 2 study evaluating the efficacy and safety of the anti-IGF-1R antibody cixutumumab in patients with previously treated advanced or metastatic soft-tissue sarcoma or Ewing family of tumours

BackgroundCixutumumab (IMC-A12), a fully human immunoglobulin G1 (IgG1) monoclonal antibody, exerts preclinical activity in several sarcoma models and may be effective for the treatment of these tumours.MethodsIn this open-label, multicentre, phase 2 study, patients with previously treated advanced or metastatic rhabdomyosarcoma, leiomyosarcoma, adipocytic sarcoma, synovial sarcoma or Ewing family of tumours received intravenous cixutumumab (10 mg/kg) for 1 h every other week until disease progression or discontinuation. The primary end-point was the progression-free survival rate (PFR), defined as stable disease or better at 12 weeks. In each tier of disease histology, Simon’s optimum 2-stage design was applied (PFR at 12 weeks P0 = 20%, P1 = 40%, α = 0.10, β = 0.10). Stage 1 enrolled 17 patients in each disease group/tier, with at least four patients with stable disease or better required at 12 weeks to proceed to stage 2.ResultsA total of 113 patients were enrolled; all tiers except adipocytic sarcoma were closed after stage 1 due to futility. The 12-week PFR was 12% for rhabdomyosarcoma (n = 17), 14% for leiomyosarcoma (n = 22), 32% for adipocytic sarcoma (n = 37), 18% for synovial sarcoma (n = 17) and 11% for Ewing family of tumours (n = 18). Median progression-free survival (weeks) was 6.1 for rhabdomyosarcoma, 6.0 for leiomyosarcoma, 12.1 for adipocytic sarcoma, 6.4 for synovial sarcoma and 6.4 for Ewing family of tumours. Among all patients, the most frequent treatment-emergent adverse events (AEs) were nausea (26%), fatigue (23%), diarrhoea (23%) and hyperglycaemia (20%).ConclusionsPatients with adipocytic sarcoma may benefit from treatment with cixutumumab. Cixutumumab treatment was well tolerated, with limited gastrointestinal AEs, fatigue and hyperglycaemia.     

Primary re-excision: the Italian experience in patients with localized soft-tissue sarcomas

Primary re-excision (PRE) is a wide, non-mutilating procedure carried out in patients with soft-tissue sarcomas (STS) when microscopic residuals are left after initial excision or when there are insufficient data on its completeness. The aim of this study was to evaluate the role of PRE in patients enrolled in two consecutive Italian studies between January 1988 and September 1999. Of 126 patients with grade IIa tumors, 53 underwent PRE (23 rhabdomyosarcomas [RMS] and 30 non-RMS STS [NRSTS]). The primary sites were the extremities in 20, paratesticular 15, trunk 9, head-neck-non-parameningeal (HNnPM) 6, bladder 1, other sites in 2; the tumor (T) status was T1a in 30, T1b in 10, T2a in 9, and T2b in 4; the median interval between primary surgery and PRE was 36 days. Of the 53 patients, 45 had complete histologic excision of the tumor (residuals were found in 21/45 specimens) and subsequently received chemotherapy (CT) alone: 39/45 are in their first complete remission (CR) with a median follow-up of 53 months; 6/45 (3 RMS, 3 NRSTS) relapsed, 4 locally (2 extremities, 2 trunk), and 1 of these died of progressive disease, and 2 with metastatic spread died of their disease. In 8/53 cases (HNnPM 4, extremities 2, bladder 1, trunk 1) PRE did not achieve complete removal of the residuals (3 T1a, 2 Tlb, 2 T2a, 1 T2b); these patients were treated with CT and/or radiotherapy (RT); 1 also underwent further surgery. PRE was able to achieve or confirm complete excision in 45/53 patients, and 39 maintained the first CR without RT. The histologic types and the presence of residuals at PRE did not predict the failures; PRE was effective especially in extremity, trunk, and paratesticular sites, whereas its role was uncertain in large sarcomas over 5 cm in size. Accepted: 16 November 2000     

Distinctive Head and Neck Bone and Soft Tissue Neoplasms

Benign and malignant primary bone and soft tissue lesions of the head and neck are rare. The uncommon nature of these tumors, combined with the complex anatomy of the head and neck, pose diagnostic challenges to pathologists. This article describes the pertinent clinical, radiographic, and pathologic features of selected bone and soft tissue tumors involving the head and neck region, including angiofibroma, glomangiopericytoma, rhabdomyosarcoma, biphenotypic sinonasal sarcoma, chordoma, chondrosarcoma, and osteosarcoma. Emphasis is placed on key diagnostic pitfalls, differential diagnosis, and the importance of correlating clinical and radiographic information, particularly for tumors involving bone.     

Alterations of <Emphasis Type="Italic">RB1</Emphasis> gene in embryonal and alveolar rhabdomyosarcoma: special reference to utility of pRB immunoreactivity in differential diagnosis of rhabdomyosarcoma subtype

PURPOSE: Rhabdomyosarcoma (RMS), which is the most common pediatric soft tissue sarcoma, is classified into two major histologic subtypes, embryonal RMS (ERMS) and alveolar RMS (ARMS). RMS is occasionally reported to be the second neoplasm of hereditary retinoblastoma. Osteosarcoma is known as the most common second neoplasm of hereditary retinoblastoma, and tumorigenesis of osteosarcoma has been proven in previous studies to be related to the RB gene (RB1) alteration. Therefore, there might be a correlation between the tumorigenesis of RMS and RB1 alteration. METHODS: We examined the RB protein (pRB) expression and RB1 alteration such as allelic imbalance (gain or loss) and homozygous deletion, using immunohistochemistry, microsatellite makers, and quantitative real-time PCR in 57 sporadic RMS. RESULTS: Allelic imbalance was more frequently detected in ERMS (13/27), than in ARMS (3/20) (P = 0.04). Homozygous deletion on the protein-binding pocket domain of RB1 was found in 6 of 27 ERMS and in 2 of 20 ARMS (P = 0.24). Furthermore, immunohistochemical pRB labeling indexes (LI) in 31 ERMS (median value, 31%) were significantly reduced in comparison with those observed in 26 ARMS (median value, 85%) (P < 0.0001). CONCLUSIONS: Our results support the assertion that tumorigenesis of RMS may be associated with RB1 alteration especially in ERMS, as previously reported for osteosarcoma. As for the RB pathway, each subtype of RMS may have a different tumorigenesis. In addition, immunohistochemical pRB LI may have the potential to be a useful ancillary tool in the differential diagnosis of RMS subtypes.     

心脏非粘液性原发肿瘤的病理学研究

我院１９６５年至１９９３年间，共检出心脏原发肿瘤２３６例，其中１６例为非粘液性肿瘤，占同期心脏原发肿瘤的６．８％。包括脉管瘤７例，间叶细胞瘤５例，间皮细胞瘤、脂肪瘤、横纹肌肉瘤及纤维弹力瘤各１例。良性和恶性肿瘤各８例。     

Matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 expression in paediatric tumour cells. Effects of tumour cell proliferation modulators on gelatinolytic activity

We have examined the expression of 72-kDa gelatinase/type IV collagenase or matrix metalloproteinase-2 (MMP-2) and ist inhibitor, tissue inhibitor of metalloproteinase-2 (TIMP-2), in various cell lines derived from paediatric tumours. In a neuroblastoma model system of tumour progression, the expression level of MMP-2 mRNA was higher in the more malignant cell line. Surprisingly, MMP-2 was not expressed in the highly malignant rhabdomyosarcoma A-204 cell line. TIMP-2 showed higher expression levels in the 007 and U-2OS tumour cell lines than in the more malignant ones, WAC2 and A-204 cells. We have also determined the effect of some tumour cell proliferation modulators on gelatinolytic activity. While basic fibroblast growth factor and retinoic acid produced no apparent change in gelatinolytic activity, genistein induced in partial inhibition of gelatinolytic activity.Abbreviations MMP matrix metalloproteinase - TIMP tissue inhibitor of metalloproteinases - bFGF basic fibroblast growth factor - GAPDH glyceraldehyde-3-phosphate dehydrogenase - ECM extracellular matrix     

Orbital rhabdomyosarcomas: A review

Rhabdomyosarcoma (RMS) is a highly malignant tumor and is one of the few life-threatening diseases that present first to the ophthalmologist. It is the most common soft-tissue sarcoma of the head and neck in childhood with 10% of all cases occurring in the orbit. RMS has been reported from birth to the seventh decade, with the majority of cases presenting in early childhood. Survival has changed drastically over the years, from 30% in the 1960’s to 90% presently, with the advent of new diagnostic and therapeutic modalities. The purpose of this review is to provide a general overview of primary orbital RMS derived from a literature search of material published over the last 10 years, as well as to present two representative cases of patients that have been managed at our institute.     

A clinical study of nasopharyngeal masses

Out of 36511 patients attending the ENT OHD of R. G,. Aur Medical Callege & Hospital. Kolkata, in one year 0.08% patients were found tuning naspharyngeal mass. 30 cases of nasopharyngeal mass were studied. The peak incidence of nasopharyngeal mass was in the age group between II to 20 years (40%). The incidence in males (73%) was more than females(27%). The maximum ineldence was found among students (74%). Commonest ntuopharyngeal nuns teas antrochoanal polyp (30%). Next commlon masses were adenoids (23%)Juvenile angwfibroma(20%) and nasophartngeal carcinoma (13%). Nasal obstruction was the main presenting symptom(83%) followed by epistaxis (40%).