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Open AccessArticle

Head and Neck Sarcomas: A Comprehensive Cancer Center Experience

by Mohamedtaki A. Tejani, Thomas J. Galloway, Miriam Lango, John A. Ridge and Margaret Von Mehren

Cancers 2013, 5(3), 890-900; https://doi.org/10.3390/cancers5030890 - 15 Jul 2013

Cited by 48 | Viewed by 6802

Abstract

Head/neck sarcomas are rare, accounting for about 1% of head/neck malignancies and 5% of sarcomas. Outcomes have historically been worse in this group, due to anatomic constraints leading to difficulty in completely excising tumors, with high rates of local recurrence. We retrospectively analyzed [...] Read more.

Head/neck sarcomas are rare, accounting for about 1% of head/neck malignancies and 5% of sarcomas. Outcomes have historically been worse in this group, due to anatomic constraints leading to difficulty in completely excising tumors, with high rates of local recurrence. We retrospectively analyzed cases of head/neck soft tissue sarcomas (STS) and osteogenic sarcomas managed in a multi-disciplinary setting at Fox Chase Cancer Center from 1999–2009 to describe clinicopathologic characteristics, treatment, outcomes, and prognostic factors for disease control and survival. Thirty patients with STS and seven patients with osteogenic sarcoma were identified. Most STS were high grade (23) and almost all were localized at presentation (28). Common histologies were synovial cell (6), rhabdomyosarcoma (5), angiosarcoma (4), liposarcoma (4) and leiomyosarcoma (3). The type of primary therapy and disease outcomes were analyzed. Cox proportional hazards regression analysis was performed to identify predictors of disease-free survival (DFS) and overall survival (OS). The HR and 95% CI for Cox model and median DFS/OS analyzed by Kaplan-Meier curves were calculated. Full article

(This article belongs to the Special Issue Soft Tissue and Bone Sarcoma)

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Open AccessArticle

A Phase I Study of the Combination of Temsirolimus with Irinotecan for Metastatic Sarcoma

by Claire F. Verschraegen, Sujana Movva, Yongli Ji, Berndt Schmit, Robert H. Quinn, Ben Liem, Therese Bocklage and Monte Shaheen

Cancers 2013, 5(2), 418-429; https://doi.org/10.3390/cancers5020418 - 11 Apr 2013

Cited by 7 | Viewed by 6591

Abstract

mTOR inhibitors are emerging as important anti-neoplastic agents with a wide range of clinical applications. The topoisomerase I inhibitor irinotecan is a potent DNA damaging drug, with a broad spectrum of anticancer activities. mTOR appears to enhance cancer cell survival following DNA damage, [...] Read more.

mTOR inhibitors are emerging as important anti-neoplastic agents with a wide range of clinical applications. The topoisomerase I inhibitor irinotecan is a potent DNA damaging drug, with a broad spectrum of anticancer activities. mTOR appears to enhance cancer cell survival following DNA damage, thus the inhibition of mTOR after irinotecan could theoretically show synergistic activities in patients. Both mTOR inhibitors and irinotecan have been used as single agents in soft tissue sarcomas with limited efficacy. We completed a phase I trial of the combination of the mTOR inhibitor, temsirolimus, and irinotecan in patients with advanced soft tissue sarcoma. Seventeen patients were recruited. The Phase II recommended dose is 20 mg of temsirolimus and 80 mg/m² of irinotecan administered on weekly basis for three out of four weeks. Most frequently encountered toxicities include cytopenias, fatigue, and gastrointestinal toxicities. Two patients (one with leiomyosarcoma and one with high grade undifferentiated sarcoma) had stable disease for more than 12 months. Full article

(This article belongs to the Special Issue Soft Tissue and Bone Sarcoma)

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Open AccessArticle

Ex Vivo Behaviour of Human Bone Tumor Endothelial Cells

by Teresa Infante, Elena Cesario, Michele Gallo, Flavio Fazioli, Annarosaria De Chiara, Cristina Tutucci, Gaetano Apice and Filomena De Nigris

Cancers 2013, 5(2), 404-417; https://doi.org/10.3390/cancers5020404 - 11 Apr 2013

Cited by 4 | Viewed by 6316

Abstract

Cooperation between endothelial cells and bone in bone remodelling is well established. In contrast, bone microvasculature supporting the growth of primary tumors and metastasis is poorly understood. Several antiangiogenic agents have recently been undergoing trials, although an extensive body of clinical data and [...] Read more.

Cooperation between endothelial cells and bone in bone remodelling is well established. In contrast, bone microvasculature supporting the growth of primary tumors and metastasis is poorly understood. Several antiangiogenic agents have recently been undergoing trials, although an extensive body of clinical data and experimental research have proved that angiogenic pathways differ in each tumor type and stage. Here, for the first time, we characterize at the molecular and functional level tumor endothelial cells from human bone sarcomas at different stages of disease and with different histotypes. We selected a CD31⁺ subpopulation from biopsies that displayed the capability to grow as adherent cell lines without vascular endothelial growth factor (VEGF). Our findings show the existence in human primary bone sarcomas of highly proliferative endothelial cells expressing CD31, CD44, CD105, CD146 and CD90 markers. These cells are committed to develop capillary-like structures and colony formation units, and to produce nitric oxide. We believe that a better understanding of tumor vasculature could be a valid tool for the design of an efficacious antiangiogenic therapy as adjuvant treatment of sarcomas. Full article

(This article belongs to the Special Issue Soft Tissue and Bone Sarcoma)

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Open AccessArticle

Protein Kinase C Epsilon and Genetic Networks in Osteosarcoma Metastasis

by Atta Goudarzi, Nalan Gokgoz, Mona Gill, Dushanthi Pinnaduwage, Daniele Merico, Jay S. Wunder and Irene L. Andrulis

Cancers 2013, 5(2), 372-403; https://doi.org/10.3390/cancers5020372 - 8 Apr 2013

Cited by 5 | Viewed by 7840

Abstract

Osteosarcoma (OS) is the most common primary malignant tumor of the bone, and pulmonary metastasis is the most frequent cause of OS mortality. The aim of this study was to discover and characterize genetic networks differentially expressed in metastatic OS. Expression profiling of [...] Read more.

Osteosarcoma (OS) is the most common primary malignant tumor of the bone, and pulmonary metastasis is the most frequent cause of OS mortality. The aim of this study was to discover and characterize genetic networks differentially expressed in metastatic OS. Expression profiling of OS tumors, and subsequent supervised network analysis, was performed to discover genetic networks differentially activated or organized in metastatic OS compared to localized OS. Broad trends among the profiles of metastatic tumors include aberrant activity of intracellular organization and translation networks, as well as disorganization of metabolic networks. The differentially activated PRKCε-RASGRP3-GNB2 network, which interacts with the disorganized DLG2 hub, was also found to be differentially expressed among OS cell lines with differing metastatic capacity in xenograft models. PRKCε transcript was more abundant in some metastatic OS tumors; however the difference was not significant overall. In functional studies, PRKCε was not found to be involved in migration of M132 OS cells, but its protein expression was induced in M112 OS cells following IGF-1 stimulation. Full article

(This article belongs to the Special Issue Soft Tissue and Bone Sarcoma)

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Open AccessArticle

Nuclear DNA-Content in Mesenchymal Lesions in Dogs: Its Value as Marker of Malignancy and Extent of Genomic Instability

by Kim M. Boerkamp, Gerard R. Rutteman, Marja J. L. Kik, Jolle Kirpensteijn, Christoph Schulze and Guy C. M. Grinwis

Cancers 2012, 4(4), 1300-1317; https://doi.org/10.3390/cancers4041300 - 3 Dec 2012

Cited by 1 | Viewed by 6789

Abstract

DNA-aneuploidy may reflect the malignant nature of mesenchymal proliferations and herald gross genomic instability as a mechanistic factor in tumor genesis. DNA-ploidy and -index were determined by flow cytometry in canine inflammatory or neoplastic mesenchymal tissues and related to clinico-pathological features, biological behavior [...] Read more.

DNA-aneuploidy may reflect the malignant nature of mesenchymal proliferations and herald gross genomic instability as a mechanistic factor in tumor genesis. DNA-ploidy and -index were determined by flow cytometry in canine inflammatory or neoplastic mesenchymal tissues and related to clinico-pathological features, biological behavior and p53 gene mutational status. Half of all sarcomas were aneuploid. Benign mesenchymal neoplasms were rarely aneuploid and inflammatory lesions not at all. The aneuploidy rate was comparable to that reported for human sarcomas with significant variation amongst subtypes. DNA-ploidy status in canines lacked a relation with histological grade of malignancy, in contrast to human sarcomas. While aneuploidy was related to the development of metastases in soft tissue sarcomas it was not in osteosarcomas. No relation amongst sarcomas was found between ploidy status and presence of P53 gene mutations. Heterogeneity of the DNA index between primary and metastatic sarcoma sites was present in half of the cases examined. Hypoploidy is more common in canine sarcomas and hyperploid cases have less deviation of the DNA index than human sarcomas. The variation in the presence and extent of aneuploidy amongst sarcoma subtypes indicates variation in genomic instability. This study strengthens the concept of interspecies variation in the evolution of gross chromosomal aberrations during cancer development. Full article

(This article belongs to the Special Issue Soft Tissue and Bone Sarcoma)

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Open AccessReview

Proton Radiotherapy for Pediatric Sarcoma

by Matthew M. Ladra and Torunn I. Yock

Cancers 2014, 6(1), 112-127; https://doi.org/10.3390/cancers6010112 - 14 Jan 2014

Cited by 12 | Viewed by 9984

Abstract

Pediatric sarcomas represent a distinct group of pathologies, with approximately 900 new cases per year in the United States alone. Radiotherapy plays an integral role in the local control of these tumors, which often arise adjacent to critical structures and growing organs. The [...] Read more.

Pediatric sarcomas represent a distinct group of pathologies, with approximately 900 new cases per year in the United States alone. Radiotherapy plays an integral role in the local control of these tumors, which often arise adjacent to critical structures and growing organs. The physical properties of proton beam radiotherapy provide a distinct advantage over standard photon radiation by eliminating excess dose deposited beyond the target volume, thereby reducing both the dose of radiation delivered to non-target structures as well as the total radiation dose delivered to a patient. Dosimetric studies comparing proton plans to IMRT and 3D conformal radiation have demonstrated the superiority of protons in numerous pediatric malignancies and data on long-term clinical outcomes and toxicity is emerging. In this article, we review the existing clinical and dosimetric data regarding the use of proton beam radiation in malignant bone and soft tissue sarcomas. Full article

(This article belongs to the Special Issue Soft Tissue and Bone Sarcoma)

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Open AccessReview

Novel Systemic Therapies in Advanced Liposarcoma: A Review of Recent Clinical Trial Results

by William W. Tseng, Neeta Somaiah, Alexander J. Lazar, Dina C. Lev and Raphael E. Pollock

Cancers 2013, 5(2), 529-549; https://doi.org/10.3390/cancers5020529 - 10 May 2013

Cited by 37 | Viewed by 10892

Abstract

Liposarcoma is one of the most common adult soft tissue sarcomas and consists of three histologic subtypes (well and dedifferentiated, myxoid/round cell, and pleomorphic). Surgery is the mainstay of treatment for localized disease; however for unresectable or metastatic disease, effective treatment options are [...] Read more.

Liposarcoma is one of the most common adult soft tissue sarcomas and consists of three histologic subtypes (well and dedifferentiated, myxoid/round cell, and pleomorphic). Surgery is the mainstay of treatment for localized disease; however for unresectable or metastatic disease, effective treatment options are currently limited. In the past decade, a better understanding of the distinct genetic and molecular aberrations for each of the three histologic subtypes has led to the development of several novel systemic therapies. Data from phase I and early phase II clinical trials have been reported. Despite challenges with conducting clinical trials in liposarcoma, preliminary results for several of these novel, biology-driven therapies are encouraging. Full article

(This article belongs to the Special Issue Soft Tissue and Bone Sarcoma)

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Open AccessReview

Lost in Translation: Ambiguity in Nerve Sheath Tumor Nomenclature and Its Resultant Treatment Effect

by Nicholas M. Bernthal, Kevin B. Jones, Michael J. Monument, Ting Liu, David Viskochil and R. Lor Randall

Cancers 2013, 5(2), 519-528; https://doi.org/10.3390/cancers5020519 - 8 May 2013

Cited by 8 | Viewed by 5971

Abstract

There is much ambiguity surrounding the diagnosis of nerve sheath tumors, including atypical neurofibroma and low-grade MPNST, and yet, the distinction between these entities designates either benign or malignant behavior and thus carries presumed profound prognostic importance that often guides treatment. This study [...] Read more.

There is much ambiguity surrounding the diagnosis of nerve sheath tumors, including atypical neurofibroma and low-grade MPNST, and yet, the distinction between these entities designates either benign or malignant behavior and thus carries presumed profound prognostic importance that often guides treatment. This study reviews the diagnostic criteria used to designate atypical neurofibroma from low-grade MPNSTs and reviews existing literature the natural history of each of these tumors to see if the distinction is, in fact, of importance. Full article

(This article belongs to the Special Issue Soft Tissue and Bone Sarcoma)

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Open AccessReview

Hypoxia-Inducible Factors: Mediators of Cancer Progression; Prognostic and Therapeutic Targets in Soft Tissue Sarcomas

by Navid Sadri and Paul J. Zhang

Cancers 2013, 5(2), 320-333; https://doi.org/10.3390/cancers5020320 - 2 Apr 2013

Cited by 48 | Viewed by 10666

Abstract

Soft-tissue sarcomas remain aggressive tumors that result in death in greater than a third of patients due to either loco-regional recurrence or distant metastasis. Surgical resection remains the main choice of treatment for soft tissue sarcomas with pre- and/or post-operational radiation and neoadjuvant [...] Read more.

Soft-tissue sarcomas remain aggressive tumors that result in death in greater than a third of patients due to either loco-regional recurrence or distant metastasis. Surgical resection remains the main choice of treatment for soft tissue sarcomas with pre- and/or post-operational radiation and neoadjuvant chemotherapy employed in more advanced stage disease. However, in recent decades, there has been little progress in the average five-year survival for the majority of patients with high-grade soft tissue sarcomas, highlighting the need for improved targeted therapeutic agents. Clinical and preclinical studies demonstrate that tumor hypoxia and up-regulation of hypoxia-inducible factors (HIFs) is associated with decreased survival, increased metastasis, and resistance to therapy in soft tissue sarcomas. HIF-mediated gene expression regulates many critical aspects of tumor biology, including cell survival, metabolic programming, angiogenesis, metastasis, and therapy resistance. In this review, we discuss HIFs and HIF-mediated genes as potential prognostic markers and therapeutic targets in sarcomas. Many pharmacological agents targeting hypoxia-related pathways are in development that may hold therapeutic potential for treating both primary and metastatic sarcomas that demonstrate increased HIF expression. Full article

(This article belongs to the Special Issue Soft Tissue and Bone Sarcoma)

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