Substantial Volume Changes and Plan Adaptations During Preoperative Radiation Therapy in Extremity Soft Tissue Sarcoma Patients

Purpose

Many authors suggest that extremity soft tissue sarcomas (ESTS) do not change significantly in size during preoperative radiation therapy (RT). This cone beam computed tomography study investigates the justification to deliver the entire course with 1 initial RT plan by observing anatomic changes during RT.

The Role of Radiation Therapy in the Treatment of Sarcoma of Soft Tissue

The treatment of sarcomas of soft tissue has evolved considerably over the years. Initially, as these tumors were often pseudoencapsulated, it was thought that a local excision might be adequate in producing local tumor control. As it was shown that there was a high incidence of local recurrence after local excision alone, surgeons began to treat these tumors with more aggressive resections. Thus, many surgeons began performing amputations at the joint above the tumor in order to maximize local control. Radiation therapy was seldom used as these tumors were thought to be radioresistant. However, over the last 20 years it has become apparent that sarcomas of soft tissue are not radioresistant, and microscopic disease can be controlled in a high percentage of patients with the use of high-dose radiation. Even bulky tumor masses can occasionally be controlled with radiation alone. Thus, there has been a gradual change in treatment policy so that many patients are now treated with the combination of a local resection and radiation therapy. This approach utilizes the ability of the surgical resection to remove the gross tumor and radiation therapy to eradicate microscopic tumor extensions.     

New Developments in Targeted Therapy for Soft Tissue Sarcoma

Soft tissue sarcomas (STS) are rare diseases, with an estimated 10,390 new cases in the United States in 2008. Unfortunately, only 50% are cured with surgical resection. The standard cytotoxic chemotherapeutic agents have not been successful in the treatment of metastatic disease. The standard single-agent chemotherapy for metastatic disease is doxorubicin, with only 20% to 25% response rates. The combination of doxorubicin with other agents, such as ifosfamide, has improved response rates, without any improvement in overall survival. New targeted therapies have shown some activity in STS; however, disease stabilization is seen more often than a true radiographic response. The combination of cytotoxic chemotherapy with more targeted and novel agents may be appropriate to improve outcome in these patients. The agents of interest in sarcomas at this time are multi-tyrosine kinase inhibitors, antiangiogenesis agents, inhibitors of mammalian target of rapamycin, hypoxia-activating prodrugs, insulin growth factor monoclonal antibodies, and tumor necrosis factor-related apoptosis-inducing ligand agonists.     

Dosimetric Comparison of Volumetric Modulated Arc Therapy and Intensity Modulated Radiation Therapy for Soft Tissue Sarcoma of the Extremities

PurposeRadiation therapy is a standard part of limb conserving therapy for extremity soft tissue sarcoma (STS) at high risk of recurrence. Toxic effects increase with radiation dose and volume of normal tissue irradiated. This study sought to compare dosimetry of volumetric modulated arc therapy (VMAT) with intensity modulated radiation therapy (IMRT) and to investigate the optimal planning technique.Methods and MaterialsTwenty patients with extremity STS who underwent preoperative radiation therapy (50 Gy in 25 fractions) between 2016 and 2020 at a specialised sarcoma center were included. The original treatment techniques were sliding window IMRT or 3-dimensional conformal. VMAT plans were retrospectively generated according to the original tumor and organ-at-risk constraints. Quality assurance was performed as per departmental protocol. Wilcoxon signed-rank test was used to compare dosimetric parameters (for planning target volume [PTV], in-field bone, and soft tissue structures), monitor units (MUs), and treatment time.ResultsMedian patient age was 65 years and the majority were male (n = 14, 70%). The most common subtype was undifferentiated pleomorphic sarcoma (n = 14, 70%), and most tumors were located on the thigh (n = 12, 60%). Median PTV was 1110 cm³ and median volume of in-field bone 236 cm³. VMAT plans had significantly lower average MU (480 vs 862 MU, P < .001) and overall treatment time (300 vs 153 seconds, P < .001). PTV coverage favored VMAT, with marginally higher mean, minimum, and maximum doses and higher conformity index. However, differences were not statistically significant. Dose to infield bone and soft tissue structures were similar or slightly lower with VMAT.ConclusionsIn extremity STS, VMAT plans demonstrated a favorable trend toward tumor coverage and dose conformity compared with IMRT along with significantly lower MUs and half the overall treatment time.     

Histology-Specific Therapy for Advanced Soft Tissue Sarcoma and Benign Connective Tissue Tumors

OPINION STATEMENT: Molecularly targeted agents have shown activity in soft tissue sarcoma (STS) and benign connective tissue tumors over the past ten years, but response rates differ by histologic subtype. The field of molecularly targeted agents in sarcoma is increasingly complex. Often, clinicians must rely on phase II data or even case series due to the rarity of these diseases. In subtypes with a clear role of specific factors in the pathophysiology of disease, such as giant cell tumor of the bone and diffuse-type tenosynovial giant cell tumor, it is reasonable to treat with newer targeted therapies, when available, in place of chemotherapy when systemic treatment is needed to control disease. In diseases without documented implication of a pathway in disease pathogenesis (e.g. soft tissue sarcoma and vascular endothelial growth factor), clear benefit from drug treatment should be established in randomized phase III trials before implementation into routine clinical practice. Histologic subtype will continue to emerge as a critical factor in treatment selection as we learn more about the molecular drivers of tumor growth and survival in different subtypes. Many of the drugs that have been recently developed affect tumor growth more than survival, therefore progression-free survival may be a more clinically relevant intermediate endpoint than objective response rate using Response Evaluation Criteria In Solid Tumors (RECIST) in early phase sarcoma trials. Because of the rarity of disease and increasing need for multidisciplinary management, patients with connective tissue tumors should be evaluated at a center with expertise in these diseases. Participation in clinical trials, when available, is highly encouraged.     

Radiation Therapy for Treatment of Soft Tissue Sarcoma in Adults: Executive Summary of an ASTRO Clinical Practice Guideline

PurposeThis guideline provides evidence-based recommendations addressing the indications for radiation therapy (RT), sequencing of local therapies, and appropriate dose and planning techniques for management of primary, operable, localized, soft tissue sarcoma (STS) in adults.MethodsThe American Society for Radiation Oncology convened a task force to address 5 key questions focused on the use of RT for management of STS. These questions included indications for RT for STS of the extremity and superficial trunk; considerations for sequencing of RT with respect to surgery, dose of RT, appropriate treatment volumes and techniques; and the role of RT in management of retroperitoneal sarcoma. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength.ResultsMultidisciplinary evaluation and decision making are recommended for all cases of STS. RT is recommended for patients in whom there is increased risk of local recurrence of resected STS, particularly if close or microscopically positive margins are anticipated or have occurred. When RT is indicated, preoperative RT is strongly recommended over postoperative RT. Postoperative RT is conditionally recommended in specific clinical circumstances (eg, uncontrolled pain or bleeding) or when the risk of wound complications outweighs that of late toxicity from RT. Routine use of RT in addition to oncologic resection for retroperitoneal sarcoma is conditionally not recommended. When RT is used for retroperitoneal sarcoma, preoperative RT is recommended, whereas postoperative RT is not recommended.ConclusionsBased on currently published data, the American Society for Radiation Oncology task force has proposed evidence-based recommendations regarding the use of RT for STS in adults. Future studies will ascertain whether alterations in dosing and sequencing may optimize outcomes and quality of life.     

四肢软组织肉瘤术前与术后放疗临床观察

[目的]探讨四肢软组织肉瘤术前与术后放疗时间的选择及并发症情况.[方法]回顾分析43例四肢软组织肉瘤病人,其中21例术前行放射治疗(25Gy/5F),22例术后行放射治疗(66Gy/33F),观察两组病人疗效及术后伤口并发症的发生率.[结果]平均随访3.5年,术前放疗者总的生存情况稍好于术后放疗者(P＜0.05);但术前放疗者发生伤口并发症8例(38%),而术后放疗者4例(18%);而且肿瘤大小和解剖位置与并发症有关.[结论]由于术前放疗比术后放疗有较高的伤口并发症发生率,四肢软组织肉瘤治疗时应该考虑放疗的时间选择,同时考虑肿瘤大小及解剖位置.     

Targeted Therapy in Bone and Soft Tissue Sarcoma in Children and Adolescents

Pediatric soft-tissue and bone sarcomas are a heterogeneous group of tumors of mesenchymal origin which affect approximately 1,500 children in the United States each year. Using multimodal therapy (surgery, radiation, and chemotherapy), the overall 5-year survival rate for children with soft-tissue and bone sarcomas is approximately 60%–70%. However, the prognosis for children with metastatic or recurrent disease is poor; and, furthermore, the improvements in the overall cure rate have slowed. It is highly unlikely that further advances in the treatment of pediatric soft-tissue and bone sarcomas will come from traditional cytotoxic chemotherapy. Based on research advances in understanding the biology of pediatric soft-tissue and bone sarcomas, improved cure rates will likely be driven by new types of treatment which target the specific abnormalities within these tumors. These new targeted therapies may include small molecules, antibodies, or other immunotherapies. This review briefly describes the biology of the major types of pediatric sarcomas, discusses potential targets for new therapy, and highlights some recent and current clinical trials using targeted therapy.     

Updates in Pathology for Retroperitoneal Soft Tissue Sarcoma

Retroperitoneal tumors are extremely rare. More than 70% of primary retroperitoneal soft tissue tumors are malignant. The most common sarcomas in the retroperitoneum include liposarcomas and leiomyosarcoma, however other sarcomas, along with benign mesenchymal tumors, can occur. Sarcomas are a heterogenous group of tumors with overlapping microscopic features, posing a diagnostic challenge for the pathologist. Correct tumor classification has become important for prognostication and the evolving targeted therapies for sarcoma subtypes. In this review, the pathology of retroperitoneal soft tissue sarcomas is discussed, which is important to the surgical oncologist. In addition, less common sarcomas and benign mesenchymal tumors of the retroperitoneum, which may mimic sarcoma clinically and pathologically, are also discussed.     

软组织肉瘤外科治疗进展

摘 要：软组织肉瘤是发生于骨以外间叶组织的肿瘤,其亚型超过50种,可以发生在身体许多部位。软组织肉瘤的解剖位置非常重要,因为它与疾病的治疗及疗效相关。手术切除是软组织肉瘤的主要治疗方式。近几十年人们对不同亚型软组织肉瘤的自然进程有了更好的了解,软组织肉瘤的外科治疗也发生了重要的变化。全文旨在综述近年来四肢软组织肉瘤、腹膜后软组织肉瘤、胃肠间质瘤和其他软组织肉瘤的外科治疗进展。