Management of childhood malignant peripheral nerve sheath tumor

Malignant peripheral nerve sheath tumor (MPNST) is rare, but is one of the most frequent non-rhabdomyosarcoma soft-tissue sarcomas in the pediatric population. These tumors occur most frequently at axial sites and are characterized by local aggressiveness and a propensity to metastasize. They are often associated with neurofibromatosis type 1 (NF-1): the lifetime risk of patients with NF-1 developing MPNST has been estimated at 8-13%, compared with 0.001% in the general population. Because of the rarity of this tumor, little information is available on its clinical management, particularly in the pediatric age group. In a recent report on the clinical findings and treatment outcomes from a large number of children and adolescents with MPNST in an Italian and German series, less satisfactory overall outcomes than those for other pediatric sarcomas were described. Therefore, the approach to the treatment of patients with MPNST should be aggressive and risk adapted, and is necessarily complex. Patients should be referred to selected institutions with adequate experience in treating soft-tissue sarcomas, and with the multidisciplinary skills for enrolling patients in clinical trials. Surgical resection represents the mainstay of treatment, while the role of adjuvant treatment is not yet clear. Post-operative radiotherapy seems to have a role in improving local control, although the potential morbidity of irradiation should be taken into account, particularly when treating children. Although lack of local control is the major cause of treatment failure, MPNST may give rise to distant metastases. These tumors are usually considered as having uncertain chemosensitivity, but recent evidence suggests that there may be a role for chemotherapy in patients with a high-grade histology. For the near future, our hopes lie in the development of novel tailored therapies directed specifically against the molecular targets of the neoplastic cells: soft-tissue sarcomas seem particularly promising candidates for targeted therapy.     

Xenograft and genetically engineered mouse model systems of osteosarcoma and Ewing's sarcoma: tumor models for cancer drug discovery

Introduction: There are > 75 histological types of solid tumors that are classified into two major groups: bone and soft-tissue sarcomas. These diseases are more prevalent in children, and pediatric sarcomas tend to be highly aggressive and rapidly progressive. Sarcomas in adults may follow a more indolent course, but aggressive tumors are also common. Sarcomas that are metastatic at diagnosis, or recurrent following therapy, remain refractory to current treatment options with dismal overall survival rates. A major focus of clinical trials, for patients with sarcoma, is to identify novel and more effective therapeutic strategies targeted to genomic or proteomic aberrations specific to the malignant cells. Critical to the understanding of the potential for targeted therapies are models of disease that are representative of clinical disease and predictive of relevant clinical responses.

Areas covered: In this article, the authors discuss the use of mouse xenograft models and genetically engineered mice in cancer drug discovery. The authors provide a special focus on models for the two most common bone sarcomas: osteosarcoma (OS) and Ewing's sarcoma (ES).

Expert opinion: Predicting whether a new anticancer agent will have a positive therapeutic index in patients with OS and ES remains a challenge. The use of mouse sarcoma models for understanding the mechanisms involved in the response of tumors to new treatments is an important step in the process of drug discovery and the development of clinically relevant therapeutic strategies for these diseases.     

Systemic treatment options for patients with refractory adult-type sarcoma beyond anthracyclines

For the subgroup of patients with inoperable gastrointestinal stromal tumors, progress has been made by the rapid development and approval of the targeted therapy imatinib mesylate. Small round cell sarcoma, such as Ewing/PNET, desmoplastic small round cell sarcoma and rhabdomyosarcoma, are chemotherapy-sensitive and potentially curable malignancies, which are treated with multimodality, dose-intensitive and neoadjuvant protocols regardless of size or overt metastatic disease. A limited number of effective agents available for the treatment of patients with metastatic adult soft-tissue sarcoma exists, which have failed anthracyline and ifosfamide-based chemotherapy. Most other high-grade (grading >I) so-called adult-type soft-tissue sarcomas such as fibro, lipo, pleomorphic and synovial sarcoma are treated with a anthracycline-based regimen with or without ifosfamide as front-line therapy. In this review, the therapeutic activities of drugs currently available as second-line treatment in patients with metastatic soft tissue sarcoma are summarized, providing an overview of contentious or emerging treatment issues. In relapsed 'adult-type' soft-tissue sarcomas trofosfamide, gemcitabine and ecteinascidin (ET-743) appear to be drugs associated with moderate activity and an acceptable toxicity profile. An interesting finding to be noted is that the different drugs have particular effects in distinct subtypes of soft-tissue sarcoma; however, it has to be taken into account that the number of patients included in those phase II trials are limited. The role of the newer agents (e.g. patupilone derivates, brostallicin) is currently not definable. The so-called selective therapy targeting vascular endothelial growth factor (receptor), epidermal growth factor receptor, c-kit, Raf kinase or platelet-derived growth factor receptor and bcl-2 antisensing, proteasome, protein kinase C/B, and mammalian target of rabamycin inhibition will continue to be tested in gastrointestinal stromal tumors patients refractory to imatinib mesylate as well as in selected sarcoma subtypes.     

Targeted therapies in bone sarcomas: current approach and future directions

INTRODUCTION: Bone sarcomas are rare malignancies and once advanced, there is limited response to current chemotherapeutic regimens. Targeted therapies could have substantial impact on these diseases. AREAS COVERED: Specific molecular targets of bone sarcomas are reviewed along with the various targeted therapies that have potential to change the outcome of these chemotherapy resistant diseases. EXPERT OPINION: There are promising pathways identified that targeted inhibitors could provide better treatment options for metastatic bone sarcomas. There is a strong need for continued Phase II and III clinical trials investigating these molecularly targeted therapies.     

Pharmacotherapy of sarcoma

Background: Comprising < 1% of adult malignancies and approximately 12% of pediatric malignancies, sarcomas are derived from a variety of connective tissues and exhibit highly variable responsiveness to therapy. The clinical and biologic heterogeneity of the > 50 histologic subtypes of sarcomas often require different therapeutic approaches. Objective: This review describes the use of therapeutic agents in the management of bone and soft-tissue sarcomas. Methods: Relevant literature is identified and presented from major conference proceedings, as well as using the PubMed search engine. Results/conclusions: Chemotherapy has improved outcomes over the past few decade, particularly in patients with certain bone sarcomas and gastrointestinal stromal tumors; while in the majority of patients, additional strategies are necessary.     

Targeting apoptosis resistance in rhabdomyosarcoma

Resistance of human cancers to current treatment approaches remains a challenge in oncology. Therefore, there has been much interest in identifying molecular pathways that are responsible for primary or acquired resistance of cancers. Since most anticancer therapies, i.e. chemotherapy or radiotherapy, primarily act by triggering programmed cell death (apoptosis) in cancer cells, defects in apoptosis programs may confer resistance. Evasion of apoptosis in rhabdomyosarcoma may be caused by the dominance of cell survival pathways, for example aberrant activation of the PI3K/Akt/mTOR cascade, or alternatively, by defective expression or function of critical mediators of apoptosis, i.e. components of the TRAIL signaling system. In addition, signaling to apoptosis can be blocked under hypoxia, a characteristic feature of most solid tumors including rhabdomyosarcoma that has been associated with poor treatment response. Thus, molecular targeted therapies that are specifically directed to the defects in apoptosis programs, open novel perspectives to restore apoptosis sensitivity in rhabdomyosarcoma.     

New agents in the treatment of soft-tissue sarcomas

The list of agents with significant activity in soft-tissue sarcomas is very short and arguably, only includes doxorubicin and ifosfamide. Several other agents such as dacarbazine, cisplatin and etoposide, to name but a few, have marginal activity and are sometimes used in combination regimes. The need for the identification of new agents with activity against this disease is therefore paramount. Soft-tissue sarcomas are very rare and diverse and as a result, new drug trials are few and far fetched. The conventionally conducted Phase II trials, which include all histologies of soft-tissue sarcomas, run the risk of an inadequate assessment of the new drug in individual subsets, which may have variable biological behaviours. On the other hand, histology-specific Phase II trials are fraught with the problems of length due to the infrequent nature of the disease and the considerable running costs. The end result is that in this era of cost-containment, soft-tissue sarcomas are not high on the priority list of many funding agencies, thus explaining the lack of any significant progress over the past two decades. Efforts at optimising the dose intensity and schedule of administration of doxorubicin and ifosfamide, have resulted in superior activity when combined and improvement in the survival of patients with high-risk localised disease. However, efforts at identifying new agents with adequate activity have not had much success. Patients, physicians and pharmaceutical industries must be encouraged to participate in multidisciplinary clinical trials in order to improve cure rates for patients with advanced disease.     

New agents in the treatment of soft-tissue sarcomas

The list of agents with significant activity in soft-tissue sarcomas is very short and arguably, only includes doxorubicin and ifosfamide. Several other agents such as dacarbazine, cisplatin and etoposide, to name but a few, have marginal activity and are sometimes used in combination regimes. The need for the identification of new agents with activity against this disease is therefore paramount. Soft-tissue sarcomas are very rare and diverse and as a result, new drug trials are few and far fetched. The conventionally conducted Phase II trials, which include all histologies of soft-tissue sarcomas, run the risk of an inadequate assessment of the new drug in individual subsets, which may have variable biological behaviours. On the other hand, histology-specific Phase II trials are fraught with the problems of length due to the infrequent nature of the disease and the considerable running costs. The end result is that in this era of cost-containment, soft-tissue sarcomas are not high on the priority list of many funding agencies, thus explaining the lack of any significant progress over the past two decades. Efforts at optimising the dose intensity and schedule of administration of doxorubicin and ifosfamide, have resulted in superior activity when combined and improvement in the survival of patients with high-risk localised disease. However, efforts at identifying new agents with adequate activity have not had much success. Patients, physicians and pharmaceutical industries must be encouraged to participate in multidisciplinary clinical trials in order to improve cure rates for patients with advanced disease.     

Emerging drugs to treat juvenile idiopathic arthritis

Introduction: Juvenile idiopathic arthritis (JIA) differs markedly from adult rheumatoid arthritis (RA). It is not a single disease, but an exclusion diagnosis that gathers together all forms of arthritis that begin before the age of 16 years, persist for > 6 weeks and are of unknown origin. This heterogeneous group of disorders has been classified on clinical and laboratory features to try to identify homogeneous, mutually exclusives categories. While some of them appear to represent rather homogenous entities others still seem to include heterogeneous conditions. Areas covered: The advent of new biological treatments has dramatically changed both the observed responses to treatment and the expectations of therapies. The implementation of an adequate legislation as well as the presence of international research networks of pediatric rheumatology have contributed to foster the conduct of controlled clinical trials and the development of validated outcome measures. Expert opinion: Despite these progresses, there are still many problems to be solved to provide a better treatment for those patients who fail to adequately respond to current therapies. Some of the new drugs that are under investigation for RA could also be suitable in the future for improving the treatment of JIA.     

Classification of sarcomas using bioinformatics and molecular profiling

Recent advances in genomic and proteomic technologies have revolutionized our way of classifying cancers. These high-throughput technologies allow the use of powerful and multivariate bioinformatic approaches to develop molecular classifiers. These classifiers can then be used to distinguish different types of tumors based on their molecular profiles. This is particularly important for heterogeneous groups of tumors such as sarcomas. Although sarcomas have a variety of histological appearances, the distinction among some of the diagnostic groups is vague. Therefore, molecular classification provides a new way to distinguish histologically similar but molecularly different types of sarcomas, and hence improves tumor diagnosis and stratification. In addition, identification of discriminatory genes that carry information to differentiate clinical subtypes of sarcomas will further elucidate the underlying molecular pathways and pathological mechanisms of these tumors. In this article, we review some current methods used in genomic and proteomic profiling, outline the approach of using bioinformatic techniques to develop a molecular classifier, and discuss some recent examples to illustrate the use of molecular classification to distinguish different types of sarcomas and understand the biology of these tumors.     

Optimal management strategies for rhabdomyosarcoma in children

Rhabdomyosarcoma is the most common sarcoma of childhood. Fortunately, the goal of cure is realistic for the majority of patients with localized tumors. However, management of these patients remains challenging. The fact that the tumor arises in a wide variety of primary sites, some of which are associated with specific patterns of local invasion, regional lymph node spread, and therapeutic response, requires physicians to be familiar with site-specific staging and treatment details. In addition, rhabdomyosarcoma requires multimodality therapy that can be associated with significant acute toxicities and long-term effects, particularly when administered to young children. These factors sometimes present a dilemma as to the best approach to optimize the chance of cure, minimize toxicity, and respect quality of life. The purpose of this review is to discuss 'optimal' management of this complicated tumor. Since the tumor is relatively rare, requires highly specialized care, and important management questions remain to be answered, optimal management of rhabdomyosarcoma includes enrollment in clinical trials whenever possible. Appropriate management begins with establishing the correct pathologic diagnosis, histologic subtype, primary site, extent of disease (International Society of Pediatric Oncology [SIOP]-TNM-Union Internationale Contre le Cancer stage or Intergroup Rhabdomyosarcoma Study Group [IRSG] stage), and extent of resection (IRSG group). Cooperative groups throughout North America and Europe have defined risk-adapted treatment based on these factors; this treatment requires a coordinated management plan that includes surgery, chemotherapy, and usually radiotherapy. The surgical approach for rhabdomyosarcoma is to excise the primary tumor whenever possible without causing major functional or cosmetic deficits. Wide excision is difficult in some primary sites and can be complicated by the fact that the tumor grows in a locally infiltrative manner so that complete resection is often neither possible nor medically indicated. Incompletely resected tumors are generally treated with radiotherapy. The cooperative groups reduce the dose of radiation based on the response of the tumor to chemotherapy and delayed primary resection to differing degrees. Response-adjusted radiation administration may reduce the long-term effects of radiotherapy, such as bone growth arrest, muscle atrophy, bladder dysfunction, and induction of second malignant neoplasms; however, it may also be associated with an increased risk of tumor recurrence. All patients with rhabdomyosarcoma require chemotherapy. A backbone of vincristine and dactinomycin with either cyclophosphamide (VAC) or ifosfamide (IVA) has been established. Risk-adapted treatment involves reducing or eliminating the alklyating agent for patients with the most favorable disease characteristics. Clinical trials are ongoing to improve outcomes for higher risk patients; newer agents, such as topotecan or irinotecan, in combination with VAC or use of agents in novel ways are being investigated. Acute and long-term toxicities associated with these chemotherapy regimens include myelosuppression, febrile neutropenia, hepatopathy, infertility, and second malignant neoplasms. A 5-year survival rate >70% has been achieved in recent trials for patients with localized rhabdomyosarcoma. However, the outcome for patients who present with metastatic disease remains poor. In the future, risk-adapted classification of rhabdomyosarcoma will likely be based on biologic features, such as the presence of chromosomal translocations or specific gene expression profiles. It is hoped that newer therapies directed at specific molecular genetic defects will benefit all patients with rhabdomyosarcoma.     

Phase II study of CI-980 (NSC 635370) in patients with previously treated advanced soft-tissue sarcomas

Doxorubicin and ifosfamide are the two most active agents in the treatment of soft-tissue sarcomas. Patients whose tumors have failed these two drugs have very limited systemic therapy options. It is, therefore, important to identify newer drugs with activity against this disease. CI-980 is a synthetic mitotic inhibitor that binds to tubulin at the colchicine binding site and inhibits the polymerization of tubulin and blocks cell cycle progression in mitosis. Given its broad spectrum activity against several solid tumor models in vivo, we decided to perform a phase 2 study of this drug in previously treated soft-tissue sarcomas. A total of 18 eligible and evaluable patients were entered in the first stage of the trial. The median age was 53 yrs (range, 17–72). No objective responses have been noted. Six patients had stable disease after a median of 3.5 cycles of chemotherapy while 12 others had progressive disease. A total of 48 cycles were administered, 42 of which were administered at dose level 0 (4.5 mg/m²/d × 3). 3). The median AGC nadir was 1.2/µl (0.1–4.7) on day 10 and the median platelet nadir was 150,000/µl (31,000–338,000). Twenty cycles were complicated with grade 3–4 neutropenia and two cycles were complicated with FUO. There were no CNS toxicities. One patient had a grade 1 thrombophlebitis in 2 cycles and one other patient had a grade 4 thrombophlebitis in one cycle. In conclusion, CI-980 was well tolerated at this dose and schedule but inactive in soft-tissue sarcomas.     

Molecularly targeted therapies in adult soft tissue sarcomas: present approach and future directions

BACKGROUND: Sarcomas are rare neoplasms. Given the overwhelming chemotherapy resistance of the disease, patients with progressive and metastatic soft tissue sarcomas are ideal candidates for trials of investigational new drugs. OBJECTIVE: The authors review the molecular mechanisms underlying soft tissue sarcomas and discuss molecularly targeted therapies developed to improve the poor outcome of these uncommon tumors. METHODS: A Medline and American Society of Clinical Oncology abstract search was conducted using the keyword 'soft tissue sarcoma'. Articles and abstracts were reviewed and eligible for inclusion if they used targeted therapies for the treatment of patients with soft tissue sarcomas. Results/conclusion: Phase II clinical trials for patients with soft tissue sarcomas using novel targets and present recognized targets are ongoing and planned.     

Pharmacogenomics of pediatric acute lymphoblastic leukemia

Importance of the field: Pediatric acute lymphoblastic leukemia (ALL) represents one of the best examples of progress in disease treatment and improved outcome based in part upon the incorporation of the principles of pharmacogenomics. Throughout the past several decades, clinical scientists have continued to refine risk stratification in clinical trials with the understanding that individual patients have different subtypes of pediatric ALL that will respond to therapy in different, but predictable ways.

Areas covered in this review: Discussed in this review are the most significant findings from pharmacogenomic studies of pediatric ALL from 1989 to the present. Pharmacogenomic studies related to the drugs commonly used to treat pediatric ALL are covered in detail, including an emphasis on both genome-wide and candidate gene/pathway approaches.

What the reader will gain: Readers of this paper will acquire a detailed understanding of how pharmacogenomic studies can be integrated into clinical trials, in addition to some of the discrepancies still present in the field.

Take home message: The outcome for children with pediatric ALL has improved greatly, and this is in part due to the successful integration of data from pharmacogenomic studies into clinical trials.     

Effectiveness of chemotherapy in rhabdomyosarcoma: example of orbital primary

The survival of patients with rhabdomyosarcoma has been progressively improved with successive protocols due to the development of multidisciplinary management and the data accumulated by international groups. Orbital rhabdomyosarcoma represents 10% of all cases and affects young children (median age: 6.8 years). It is a chemosensitive and radiosensitive tumour. Chemotherapy is designed to decrease the indications for local therapy (mainly radiotherapy) responsible for a high rate of sequelae (cosmetic, functional or secondary cancer). According to the International Society of Paediatric Oncology guidelines, local therapy is not indicated as first-line treatment in case of complete remission after chemotherapy. The 10-year survival of children with non-parameningeal orbital rhabdomyosarcoma is currently 87% and identical survivals are reported by the various collaborative groups despite the use of different treatments. Despite clinical trials demonstrating the efficacy of many types of chemotherapy (cisplatin, etoposide, doxorubicin, dacarbazine), the value of adding these drugs to combination chemotherapy comprising of an alkylating agent (cyclophosphamide or ifosfamide), vincristine and dactinomycin has not been formally demonstrated in terms of survival benefit for children with rhabdomyosarcoma. The authors review these various results and compare the current guidelines for the management of orbital rhabdomyosarcoma recommended by North American and European groups.     

Effectiveness of chemotherapy in rhabdomyosarcoma: example of orbital primary

The survival of patients with rhabdomyosarcoma has been progressively improved with successive protocols due to the development of multidisciplinary management and the data accumulated by international groups. Orbital rhabdomyosarcoma represents 10% of all cases and affects young children (median age: 6.8 years). It is a chemosensitive and radiosensitive tumour. Chemotherapy is designed to decrease the indications for local therapy (mainly radiotherapy) responsible for a high rate of sequelae (cosmetic, functional or secondary cancer). According to the International Society of Paediatric Oncology guidelines, local therapy is not indicated as first-line treatment in case of complete remission after chemotherapy. The 10-year survival of children with non-parameningeal orbital rhabdomyosarcoma is currently 87% and identical survivals are reported by the various collaborative groups despite the use of different treatments. Despite clinical trials demonstrating the efficacy of many types of chemotherapy (cisplatin, etoposide, doxorubicin, dacarbazine), the value of adding these drugs to combination chemotherapy comprising of an alkylating agent (cyclophosphamide or ifosfamide), vincristine and dactinomycin has not been formally demonstrated in terms of survival benefit for children with rhabdomyosarcoma. The authors review these various results and compare the current guidelines for the management of orbital rhabdomyosarcoma recommended by North American and European groups.     

Metabolic, toxicological, and safety considerations for drugs used to treat ADHD

INTRODUCTION: Pharmacotherapy is frequently used to treat symptoms of attention-deficit/hyperactivity disorder (ADHD), the most common neurobehavioral disorder of childhood. The typically prescribed agents for ADHD have varying durations of effect and degrees of efficacy. The broad range of pharmacological treatments available allows for both single and combination therapies for achieving optimal therapeutic effects. Metabolic, toxicological, and safety information are critical for an informed evaluation of the risk/benefit considerations in prescribing practices. AREAS COVERED: This article focuses on the medications with current FDA approval for use in the treatment of ADHD in pediatric and adult populations. This review covers the stimulants (amphetamine and methylphenidate) and non-stimulants (atomoxetine, clonidine extended release, and guanfacine extended release) used to treat ADHD and presents an overview of their respective metabolic, toxicological, and safety features. A literature search and review of the relevant medications were carried out using the PubMed database up to November 2011. EXPERT OPINION: New trends in study design based on drug profiles include the use of adjuvant therapies and the inclusion of patients with comorbidities. The recent expansion of inclusion/exclusion criteria in pediatric clinical trials of ADHD allows for a more rigorous analysis of associated benefits and risks with the use of adjuvant therapy.     

Phase II study of CI-980 (NSC 635370) in patients with previously treated advanced soft-tissue sarcomas

Doxorubicin and ifosfamide are the two most active agents in the treatment of soft-tissue sarcomas. Patients whose tumors have failed these two drugs have very limited systemic therapy options. It is, therefore, important to identify newer drugs with activity against this disease. CI-980 is a synthetic mitotic inhibitor that binds to tubulin at the colchicine binding site and inhibits the polymerization of tubulin and blocks cell cycle progression in mitosis. Given its broad spectrum activity against several solid tumor models in vivo, we decided to perform a phase 2 study of this drug in previously treated soft-tissue sarcomas. A total of 18 eligible and evaluable patients were entered in the first stage of the trial. The median age was 53 yrs (range, 17–72). No objective responses have been noted. Six patients had stable disease after a median of 3.5 cycles of chemotherapy while 12 others had progressive disease. A total of 48 cycles were administered, 42 of which were administered at dose level 0 (4.5 mg/m²/d × 3). 3). The median AGC nadir was 1.2/µl (0.1–4.7) on day 10 and the median platelet nadir was 150,000/µl (31,000–338,000). Twenty cycles were complicated with grade 3–4 neutropenia and two cycles were complicated with FUO. There were no CNS toxicities. One patient had a grade 1 thrombophlebitis in 2 cycles and one other patient had a grade 4 thrombophlebitis in one cycle. In conclusion, CI-980 was well tolerated at this dose and schedule but inactive in soft-tissue sarcomas.     

儿童横纹肌肉瘤预后的影响因素分析

目的:探讨儿童横纹肌肉瘤(RMS)的临床病理特征及预后影响因素。方法:回顾性分析我科93例RMS患儿的临床及生存资料,引入患儿性别、年龄、肿瘤大小、原发部位、组织学类型、COG-stage分期、COG-group分期、危险度分组和手术情况共9个因素。采用COX回归模型进行多因素分析,确立影响预后的因素,采用Kaplan-Meier生存曲线和Log-rank检验比较影响因素与生存率的关系。结果:全组1年、3年、5年生存率分别为90.3%、62.0%、43.1%,总体中位生存期为47.28个月。多因素分析显示组织学类型、原发部位、group分期和是否手术切除是儿童RMS预后的影响因素。生存分析提示不同组织学类型、原发部位、group分期及是否手术切除的预后差异均有统计学意义(均P<0.001)。结论:儿童RMS预后的影响因素有组织学类型、原发部位、group分期和是否手术切除,通过此分析能为预后判断和临床治疗强度的选择提供依据。     

Current and advancing systemic treatment options for soft tissue sarcomas

Introduction: Soft tissue sarcomas are a collection of rare malignancies, the treatment of which has evolved over time. Although cytotoxic chemotherapy remains the cornerstone of management of metastatic disease, many new treatments have been developed or show great promise in the treatment of soft tissue sarcoma. Research into the different underlying pathogenesis of individual subtypes has driven progress in treatment. This has allowed development of treatments targeted to specific subtypes of sarcoma.

Areas covered: We provide a review of the current field of systemic therapy in soft tissue sarcoma. This is followed by an in-depth analysis of recent developments in treatment, as well as new treatments that are aimed at specific subtypes of sarcoma, and the biological rationale behind these therapies. We also look in detail at the promising new agents currently in development.

Expert opinion: Much progression has been made in treatment of soft tissue sarcomas with multiple exciting new treatments in development. However outcomes in general remain poor. Further research into the underlying pathogenesis of soft tissue sarcomas may help deliver more effective systemic therapies. Increased collaboration between basic science, translational and clinical investigators is required at national and international levels to maximise progress.