Conformal Therapy for Pediatric Sarcomas

For decades, pediatric oncology has lead the field in the implementation of combined modality therapy and has tested indications for radiation therapy in this patient population. More recently, adult experiences with conformal methods of external beam irradiation and brachytherapy have refined radiation therapy as modality and increased its attractiveness as a means to achieve local control. These refinements come at a time when the current rates of local failure for advanced stage patients with pediatric solid tumors are significant enough to warrant a reexamination of the accepted indications for radiation therapy and its sequencing and dose. Conformal methods of radiation therapy, including brachytherapy, will facilitate efforts to improve local control. These methods have a special role in the pediatric patient where the potential for dose escalation, function preservation, and decreased toxicity can be used to the benefit of these patients, making the majority of them likely to be long-term survivors.     

Advances in Therapy for Pediatric Sarcomas

Pediatric sarcomas are relatively rare malignancies individually. As a group they are typically approached with combination chemotherapies in addition to local control. Fortunately, these malignancies have been approached through careful clinical trial collaboration to define risk groups and appropriately deliver local control measures and systemic therapies. Although local disease is typically approached with curative intent, therapy typically lasts over 6 months and has significant associated morbidities. It is more difficult to cure metastatic disease or induce sustained remissions. In this article, we discuss recent advances in the understanding of the disease process and highlight recent and future cooperative group trials in osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, nonrhabdomyosarcoma soft tissue sarcomas, and desmoid tumor as well as discuss promising therapeutic approaches such as epigenetics and immunotherapy.     

Advances in Radiation Therapy for Primary and Metastatic Adult Soft Tissue Sarcomas

Soft tissue sarcomas (STS) consist of a heterogeneous group of rare malignancies arising from mesenchymal origin. While surgical resection is the primary treatment for STS, the use of radiotherapy (RT) as an adjunctive modality has been shown to improve oncologic outcomes. Technologic improvements, such as image guidance and intensity-modulated radiotherapy that significantly improve both the precision and delivery of RT, have led to the reduction of long-term RT toxicities without compromising outcomes. This review addresses these technologic advancements as well as discussing the most current updates regarding the use of brachytherapy, charged particles, and novel agents with RT.     

软组织肉瘤保存肢体的新技术应用

应用广泛切除术及高剂量率后装内照射新技术（Ｂｒａｃｈｙｔｈｅｒａｐｙ），治疗累及重要血管及神经的软组织肉瘤，达到控制预防局部复发，保存肢体功能的目的。５例肢体软组织肉瘤经治疗后均生存，随访未见局部复发及远处转移。作者介绍了保存肢体手术及肿瘤床１９２铱置管内照射的技术，同时建议对以往截肢指征应慎重考虑，只有在各种综合治疗失败情况下才考虑截肢。     

Pathology of Soft Tissue Sarcomas

Sarcomas are a rare, complex group of childhood and adult neoplasms with differentiation towards mesenchymal tissue, which may arise almost anywhere in the body. Although pathologically diverse, they frequently exhibit similar clinical presentations and radiological features. Correct histopathological diagnosis is therefore crucial, but there is overlap between histological patterns of malignant tumours, between benign and malignant lesions, and with non-mesenchymal tumours. Immunohistochemistry and molecular genetic techniques, the latter to detect tumour-specific alterations, add significantly to histological interpretation, but several groups of tumours still lack reliable immunohistochemical markers or reproducible genetic changes. The classification of sarcomas is incomplete and continues to evolve, and although the biology of many remains relatively poorly understood, our increasing insight into molecular events occurring in these tumours is certain to aid future diagnosis and therapy. This paper aims to give a broad overview of several of the main soft tissue sarcomas from a clinicopathological perspective, discussing laboratory diagnosis and the use and limitations of ancillary investigations, including recent developments in molecular diagnosis.     

New Systemic Therapy Options for Advanced Sarcomas

OPINION STATEMENT: The outcome of patients with advanced soft tissue sarcomas (STS) has not improved much during the last decade. Apart from non-pleomorphic rhabdomyosarcoma, adjuvant chemotherapy has no standard role in high risk STS. In metastatic disease little progress has been made, but during recent years much effort has been put into the development of better clinical study protocols, with stratification of patients to at least the most common histological subtypes, preventing the dilution of potential treatment efficacy when measuring results over the total heterogeneous group of STS. The outcome of patients with advanced STS is however not only dependent on the introduction of new drugs, but also on the availability of dedicated sarcoma centers in which multidisciplinary teams with the input of all experts from different disciplines, such as pathology, radiology, nuclear medicine, surgery, orthopedics radiotherapy and medical oncology is present. Long delay, wrong histological diagnoses, under- and overtreatment are not in the favor of these patients, neither with regard to outcome, nor with respect to short- and long-term toxicity. Disappointedly, centralization is not a routine part of daily care of STS patients and their care givers. Patient advocacy groups are more and more aware of the relevance of treatment in centers of expertise and are active in guiding the patients to these hospitals. At the same time the sarcoma centers should be pro-active in putting patients into clinical trials, also for rare indications within the STS group, as only in this way a better outcome for this group of patients can be reached.     

Histology-Driven Chemotherapy in Soft Tissue Sarcomas

Doxorubicin and ifosfamide are the two chemotherapy drugs that have consistently demonstrated activity in “soft tissue sarcoma” (STS). However, STS is not a homogeneous entity but an umbrella term for a diverse group of more than 40 differing subtypes; each with distinct underlying biology, natural history and response to treatments. The accuracy of the histological and in some cases molecular diagnosis is therefore critical to the optimal treatment of these patients. Leiomyosarcomas have been shown to have limited responsiveness to ifosfamide, but both the combination of gemcitabine and docetaxel, and single agent trabectedin have shown considerable activity in this tumour group. Differences in responses to chemotherapy are seen for leiomyosarcomas of different anatomical sites with uterine leiomyosarcoma demonstrating considerable chemo-responsiveness, whereas vascular leiomyosarcomas appearing far less sensitivity. There is considerable variation in the sensitivity of the three main subtypes of liposarcomas, with well-differentiated liposarcomas showing generalised chemo-resistance through to the impressive responses seen anthracyclines and to trabectedin with the myxoid subtype. Angiosarcomas have demonstrated considerable sensitivity to paclitaxel, a drug that has little activity outside of vascular sarcomas, and liposomal doxorubicin appears to have a particular indication in this subtype. Synovial sarcomas appear to have significant sensitivity to ifosfamide, even on re-challenge. On the other hand, there are subtypes that are chemo-resistant, including gastrointestinal stromal tumour, alveolar soft part sarcoma and clear cell sarcoma, and chemotherapy plays no role in their management. Whilst it is obvious that there is a need to find new agents to treat these tumours, there is an imperative to make sure that the studies that evaluate their “efficacy” are designed to determine the efficacy within differing histiotypes through stratification by histological subtype, or enrichment strategies to ensure that “activity” is not diluted by unresponsive or even chemo-resistant tumour types.     

成人原发性腹膜后软组织肉瘤

作者总结了医科院肿瘤医院收治的５０例成人原发性腹膜后软组织肉瘤的治疗经验。其中３６例行肿瘤全切除，６例肿瘤部分切除，８例探查活检术。联合脏器切除２１次，脏器损伤修补术５次。手术死亡率４％。全切除病人术后复发者占６４％，中位复发时间为１３．５个月。多数复发病人再次接受了手术治疗。用寿命表进行统计学分析，５年总累积生存期为４８％。     

软组织肉瘤分子遗传学研究进展

0 引言 软组织肉瘤是一类少见的恶性肿瘤,其组织形态学上超过50种亚型,发生率约为成人恶性肿瘤的1%,为儿童恶性肿瘤的15%.     

Experience of Interstitial Permanent I125 Brachytherapy for Extremity Soft Tissue Sarcomas

AimsSoft tissue sarcomas are uncommon, but relatively aggressive tumours. Although surgical resection remains the primary therapeutic modality for all localised tumours, brachytherapy combined with function-preserving excision is a popular treatment for extremity soft tissue sarcomas. The objective of this study was to evaluate the effect of interstitial permanent brachytherapy using I¹²⁵ seeds in patients undergoing the combined modality in the management of soft tissue sarcomas at our institution.Materials and methodsBetween January 2007 and January 2012, 110 adult patients aged 18–86 years (median = 44 years) with extremity soft tissue sarcomas and who underwent interstitial permanent brachytherapy as part of the local treatment were included in this study. Treatment included wide local excision of the tumour and brachytherapy using a permanent I¹²⁵ implantation. Complications were assessed in terms of wound complication and peripheral nerve damage.ResultsAfter a median follow-up of 43.7 months, the local control, disease-free survival and overall survival for the entire cohort studied were 74, 54 and 77%, respectively. The actual rates of wound complications requiring reoperation and nerve damage were 4.5 and 1.8%, respectively.ConclusionsWe conclude that interstitial permanent brachytherapy with I¹²⁵ after function-preserving surgery results in a satisfactory outcome in patients with extremity soft tissue sarcomas and the complication rate is low.     

肢体软组织肉瘤34例外科治疗体会

目的探讨肢体软组织肉瘤的诊断与手术疗效。方法回顾性分析外科手术治疗并经病理证实的34例肢体软组织肉瘤患者的诊治资料。结果术后病理:韧带样瘤型纤维瘤病4例,纤维肉瘤5例,浅表型纤维瘤病1例,隆突性皮肤纤维肉瘤4例,恶性纤维组织细胞瘤4例,脂肪肉瘤5例,平滑肌肉瘤5例,恶性周围神经鞘膜瘤2例,滑膜肉瘤2例,原始神经外胚层瘤2例。28例获术后随访1～4 a,4例(14.3%)复发,复发时间12～26个月,平均20个月。结论外科手术是肢体软组织肉瘤最重要的治疗手段,合理应用综合治疗和个体化治疗可提高切除率、降低复发率。     

Adjuvant Chemotherapy in Localized Soft Tissue Sarcomas: Still Not Proven

Soft tissue sarcoma is a rare and heterogeneous group of tumors in terms of histological subtypes, molecular alterations, clinical presentation, and prognosis. Yet, these tumors are most often treated similarly in the localized phase. The standard treatment of these patients requires multidisciplinary management, in particular, careful diagnostic procedures and surgery by an expert physician, preceded or followed by external radiotherapy. The utility of adjuvant chemotherapy has been explored in 14 trials comparing adjuvant chemotherapy with no treatment. Several trials reported a lower risk for local relapse and lower risk for metastatic relapse, but only a few small trials reported longer overall survival. A meta‐analysis of all trials failed to demonstrate a significant difference in the relapse‐free survival (RFS) or overall survival rates. Two additional trials, reported afterward, presented conflicting results, with a significant benefit in terms of the RFS rate for the trial of the Italian Sarcoma Group, but no difference in the RFS or overall survival rate in the most recent European Organization for Research and Treatment of Cancer trial. We conclude that adjuvant chemotherapy has not been proven to improve the outcome of an unselected population of patients. Several hypotheses are proposed to account for this observation.