Liver metastases from soft tissue sarcomas

Twenty-three patients with liver metastases from soft tissue sarcoma were reviewed. Patients with metastases to the liver first had poorer survival than those who developed spread to other sites first (P=.0035). The median time from diagnosis of the primary tumor to diagnosis of liver metastases was 14 months; the median time from diagnosis of liver metastases to death was 7 months. The median survival from diagnosis for four patients who underwent liver resection was 54 months compared to 20 months for those who did not undergo resection (NS). Soft tissue sarcomas rarely metastasize to the liver; when this occurs it is usually late in the course of the disease and after it has spread to other sites. The opportunity for successful liver resection is infrequent but may prolong survival. © 1995 Wiley-Liss, Inc.     

Imaging of sarcomas of soft tissue

Modern imaging of soft tissue sarcomas now includes ultrasounds, CT and MRI. These new techniques allow a better evaluation of initial local extension, of the response to treatment and are able to detect local recurrences early.     

Imaging and response in soft tissue sarcomas

Conventional CT and MRI scans provide exquisite anatomic detail of soft tissue sarcomas but fall short of estimating the degree of tumor viability within a sarcomatous mass. Functional imaging methods that measure biologic properties within sarcomas may be better able to determine true tumor responses to chemotherapy or radiotherapy. Many different approaches to measure biologic processes have been taken and are discussed, but positron emission tomography (PET) is currently the most quantitative and developed. A response in tumor glucose uptake, determined by PET, has been shown to correlate with improved clinical outcomes in high-grade extremity soft tissue sarcomas and gastrointestinal stromal tumors. Functional imaging of soft tissue sarcomas may prove to be useful clinically, therefore further investigation is warranted.     

The treatment and outcome of patients with soft tissue sarcomas and synchronous metastases

Introduction: There is a strong association between poor overall survival and a short disease-free interval for patients with soft tissue sarcomas (STS) and metastatic disease. Patients with STS and synchronous metastases should have a very dismal prognosis.The role of surgery in this subgroup of patients with STS has not been defined.Patients and Methods: A single-institution retrospective review was performed of 48 patients with STS and synchronous metastases in regard to patient demographics, presentation, tumor characteristics, metastatic sites, treatment, follow-up, and survival over a 27-year period.Results: Most primary tumors were >/=10 cm (58%), high-grade histology (77%), and located on the extremity (60%).The most frequent site of metastatic disease was the lung (63%); 27% of patients had metastases to >/=2 organ sites. Surgery to the primary tumor was performed in 94% of patients (n = 45) and 68% had additional radiation therapy (n = 32). Thirty- five percent of patients underwent at least one metastastectomy (n = 17). Chemotherapy was administered to 90% of patients (n = 43); 31% received >/=3 different regimens (n = 15) and 25% were given intra-arterial or intracavitary therapy (n = 12). Median overall survival was 15 months with a 21% 2-year survival. Local control of the primary tumor was achieved in 54% (n = 26), and metastastectomy was performed in 35% (n = 17). No analyzed factors were associated with an improvement in overall survivalConclusions: Despite multiple poor prognostic factors, the survival of patients with STS and metastases is comparable to those who develop delayed metastatic disease. However, unlike patients who present with metachronous disease, there was no improved survival observed for patients treated with metastastectomy. Consequently, treatment for patients with STS and synchronous metastases should be approached with caution. Surgical management of STS with synchronous metastases must be considered palliative and should be reserved for patients requiring palliation of symptoms. Patients must also be well informed of the noncurative nature of the procedure.     

Surgical treatment for skeletal metastases from soft tissue sarcomas: experience with 23 lesions in 20 patients

Purpose. This paper reports the procedures and the clinical results of a series of surgical treatments for skeletal metastases from soft tissue sarcomas.Subjects and methods. Surgical treatment of metastatic bony lesions from soft tissue sarcomas has been carried out over a 20 year period (1975-1996). Thirty-two patients developed skeletal metastases from soft tissue sarcomas, and 20 of these cases received surgical treatment. The 23 metastatic bony lesions in these 20 patients were treated using the following surgical approaches: wide resection with prosthetic replacement in five lesions, wide or marginal resection without reconstruction in four lesions, intramedullarly nailing with curettage and methylmethacrylate cementation in four lesions, marginal resection of vertebral body with replacement by a ceramic prosthesis in three lesions, laminectomy in three lesions, intramedullarly nailing in two lesions, and curettage in two lesions.Results. Relief of pain was achieved in 17 of the 20 patients. The ambulatory status of the patients with metastasis in the lower extremity or periacetabular region was significantly improved in nine of 10 cases. Seventeen patients died of disease, with a mean survival period of 17.9 months after surgery for metastasis.Discussion. Although surgical treatment for skeletal metastases from soft tissue sarcomas cannot save the life of the patient, it can be of value in improving their well-being and overall quality of life. In these cases, surgical intervention may be more frequently indicated than in tumors with an osteoblastic or mixed pattern.     

Role of chemotherapy in patients with soft tissue sarcomas

The management of soft tissue sarcomas has been highlighted in the last few years by the responsiveness of gastrointestinal stromal tumors to imatinib (Gleevec, Novartis). In this article, the use of chemotherapeutic agents in the management of this and some of the 50 or more subtypes of sarcomas are discussed, and a brief review of the use of chemotherapy in the adjuvant or neoadjuvant setting for people with large extremity sarcomas is provided. Doxorubicin and ifosfamide (Mitoxana, Bristol-Myers Squibb) remain the best individual drugs for sarcomas overall, although dacarbazine and gemcitabine (Gemzar, Eli Lilly) with or without a taxane has activity in at least a subset of sarcomas. The data regarding adjuvant chemotherapy for extremity soft tissue sarcomas is still quite mixed, with little if any overall survival advantage found to support its incorporation into disease management. The finding of tyrosine kinase inhibitors such as imatinib with demonstrated activity in gastrointestinal stromal tumors and dermatofibrosarcoma protuberans, as well as the finding of new agents such as ecteinascidin-743 (Yondelis, PharmaMar) with at least some activity against soft tissue sarcomas, reinforces the idea that we should target individual subtypes of sarcoma, just as treatment varies by subtype for the hematological malignancies.     

侵犯关节周围骨组织的软组织肉瘤外科治疗策略

目的探索侵犯关节周围骨组织的肢体软组织肉瘤的外科手术方法,并分析术后并发症、肢体功能和患者的生存状况。方法回顾性分析2004年5月至2011年10月期间,我中心所收治的30例局部侵犯关节周围骨组织的软组织肉瘤患者的临床资料。其中男14例,女16例,平均年龄51岁（17～75岁）。恶性纤维组织细胞瘤12例,脂肪肉瘤8例,原始神经外胚层肿瘤（PNET）4例,滑膜肉瘤、腺泡状软组织肉瘤和恶性神经鞘瘤2例。其中10例发病位于股骨近端,9例股骨远端,8例肱骨近端,2例胫骨近端,1例累及整个股骨。所有患者均采取了肿瘤连同受累骨组织一起广泛切除、以肿瘤型假体重建骨缺损的手术方式。术后定期复查患肢功能、x线片、肺CT等,并且密切随访,内容包括术后并发症的发生情况、肢体功能恢复情况及肿瘤学与生存状况等。结果平均随访25个月（3—84个月）,1例暂时性腓总神经麻痹;3例术后伤口愈合不良行清创手术,其中1例因深部感染不愈而截肢;2例假体断裂行翻修手术;4例肿瘤复发,局部复发率13．3％,其中1例接受截肢手术。总的肺转移为15例,且11例死亡患者中均为肺转移,其中3例合并骨转移。至最后一次随访时14例无瘤生存,5例带瘤生存,平均MSTS评分股骨近端90％,股骨远端82％,胫骨近端73％,肱骨近端71％,全股骨为60％。2年和5年生存率分别为61．6％和30．8％。结论将受累骨组织和肿瘤一起广泛切除可获得无瘤边界,降低复发率,骨缺损采用肿瘤型假体重建可恢复良好的肢体功能。巨大肢体软组织肉瘤侵犯骨组织可能是患者预后不良的因素。     

Current strategy of chemotherapy for reflactory bone and soft tissue sarcomas

Pulmonary metastases have been curative in some patients of osteosarcoma with aggressive surgical excision and intensive chemotherapy. But several retrospective studies and randomized II studies did not prove survival advantages of advanced cases with bone and soft tissue sarcoma. In treatment for refractory and advanced osteosarcoma after conventional treatments, clinical phase II trials showed 20-30% response ratio of high-dose ifosfamide and etoposide combination or carboplatin combination. In soft tissue sarcomas, high-dose ifosfamide and doxorubicin have over 50% response rate to advanced soft tissue sarcoma and total surgical excision of residual lung metastases prolong the survival. But new drugs active to refractory sarcoma had not reported in a recent decade.     

Lymph nodes as sites of metastases from sarcomas of soft tissue

Records of 323 patients with TNM Stage M0 sarcoma of soft tissue treated by the Radiation Medicine Service of the Massachusetts General Hospital over a 14-year period were reviewed to study the incidence and the implication of regional lymph node involvement. Nineteen patients (5.9%) had evidence of sarcoma metastatic to draining lymph nodes, zero of 63 (0%) were Grade 1 sarcomas, two of 118 (2%) were Grade 2, and 17 of 142 (12%) were Grade 3 sarcomas. Among patients with Grade 3 sarcomas, rhabdomyosarcoma (five of 14), vascular sarcoma (two of five), and epithelioid sarcoma (four of five) were associated with a higher incidence of lymph node involvement than synovial sarcomas (zero of four), fibrosarcomas (zero of 16), malignant fibrohistiocytomas (one of 29), neurofibrosarcomas (one of eight), liposarcomas (one of 14), and leiomyosarcomas (one of ten). From the 19 patients who had evidence of metastatic nodes, six (32%) were alive more than 58 months after the treatment of the nodes; four of six patients were without further tumor. The data of this study are compared with those cited in a review of the literature.     

Actual volume doubling time values for pulmonary metastases from soft tissue sarcomas.

Doubling time values of pulmonary metastases from soft tissue sarcomas were measured. Sixty metastases from 24 patients were measured 79 consecutive times, and, the values for 116 doubling times were calculated. Small volume metastases grew significantly faster (arithmetic mean 29.7 days) than large metastases (arithmetic mean 43.4 days). An assessment with comparative data obtained previously by measuring the doubling time values of pulmonary metastases from osteogenic sarcoma revealed similar growth characteristics. The possible involvment of identical control mechanisms operating in the growth process of pulmonary metastases in both soft tissues and osteogenic sarcomas are discussed.     

Brain metastases in soft tissue sarcomas: case report and literature review

Background and purpose: Brain metastasis is a relatively uncommon event in the natural history of soft tissue sarcomas. The increasing use of chemotherapy may have caused a reduction in local relapses as well as distant failures leading to an improvement in survival, thereby allowing metachronous seeding of the brain, a sanctuary site. The purpose of this report is to increase awareness amongst clinicians regarding such a possibility.Patients and methods: A review of the departmental sarcoma database following the presentation of this index case in the clinic.Results and discussion: An adolescent male who had previously been treated with surgery and radiotherapy for a spindle cell sarcoma of the left thigh developed a space-occupying lesion in the brain within 6 months of treatment of the primary tumor. He subsequently underwent resection of the presumed solitary brain metastasis followed by whole brain radiotherapy. On radiation he was detected to have pulmonary metastases too, for which he was offered palliative chemotherapy. The patient died of brain metastasis within 4 months. A review of the departmental sarcoma database, restricted to soft tissue sarcomas purely, maintained prospectively from 2000 till date, could not identify any other such case.Conclusion: Brain metastases from soft tissue sarcomas are rare. Patients with neurological symptoms, however, should be appropriately investigated. Surgical resection of brain metastasis could be considered for solitary brain metastasis in non-eloquent areas. Palliative radiotherapy is appropriate for patients with multiple brain metastases or co-existing extra-cranial disease.     

Adjuvant chemotherapy for soft tissue sarcomas

Soft tissue sarcomas are rare mesenchymal neoplasms with considerable heterogeneity in biologic behavior and response to systemic therapy. Most patients present with localized disease and are potentially curable with multidisciplinary treatment. In patients with a high risk of developing metastatic disease, optimal use of neoadjuvant/adjuvant therapy has a definite role in improving patient outcomes by decreasing local and distant recurrences. Histology-specific clinical trials enrolling a homogenous high-risk population have been more successful in demonstrating benefit than larger trials with unselected heterogeneous patient populations. In specific histologic subtypes responsive to chemotherapy, neoadjuvant chemotherapy with close monitoring of response is recommended.     

Follow-up in soft tissue sarcomas

The strategy for the follow-up of soft tissue sarcomas (STS) after therapy is tailored to the individual risk of recurrence and based on efficient rather than sophisticated methods of observation. Along with advances in the treatment of sarcomas, earlier detection of a less advanced and resectable recurrent disease (local or metastasis—especially to the lungs) can prolong patient survival. Since the majority of STS relapses occur within 5 years after treatment (approximately 80?% of metastases to the lung and close to 70?% of local recurrences within the first 2–3 years), in the period between 2 and 3 years after treatment, it is mandatory to follow-up patients every 3 months and perform careful history and physical examination (especially scars after surgery of the primary site) and a chest X-ray. There is no reason to perform other studies in asymptomatic patients (unless the patient reports symptoms). In case of retroperitoneal or intraperitoneal STS (including gastrointestinal stromal tumor), contrast-enhanced computed tomography of the abdomen and pelvis is recommended as the follow-up modality of choice. In this paper we outline the current recommendations for the follow-up strategy.     

间室切除在四肢软组织肿瘤治疗中的应用

目的：探讨间室切除术在四肢软组织肿瘤治疗中方法及临床价值。方法：12例四肢软组织肿瘤，上肢2例，下肢lO例，首次治疗者8例，复发者4例。行股前间室切除术3例，股后间室切除术7例，前臂外侧间室切除l例，三角肌全切除l例。伴神经部分切除术2例。功能重建包括肌腱替代和皮瓣转位等。结果：本组均保留患肢，随访10～60个月，无瘤生存10例，复发和死亡各1例。结论：对于四肢软组织肿瘤，以控制肿瘤和保存肢体为治疗核心，间室切除术系目前较理想的方法。     

Treating soft tissue sarcomas with adjuvant chemotherapy

Surgery remains the cornerstone of treatment and the only curative loco-regional approach of localized resectable soft tissue sarcoma (STS) in 2011: the usual first-line treatment is wide margin surgery plus radiotherapy, especially in the case of primary tumors arising in the limbs. An optimal initial R0 resection is one of the most reproducible and reliable prognostic factors for survival in resectable STS. Nevertheless, despite improved local control rates, more than half of the patients still develop and die from unresectable, locally advanced, and/or metastatic disease. Unfortunately, very few cytotoxic drugs have shown activity in this clinical setting with the exception of doxorubicin, ifosfamide, and to a lesser extent, dacarbazine. A conventional-dose, single-agent chemotherapy is still considered to be the standard treatment for metastatic disease. The impact of adjuvant chemotherapy after resection of a high-grade STS remains controversial due to the lack of reproducible impact on survival. Because STS is a rare disease, most trials have involved a relatively small number of patients, with heterogeneous groups of histological/molecular subtypes of sarcomas, initial sites of the disease, and patient’s characteristics. In a few trials, a lower risk for local recurrence was observed among patients receiving adjuvant chemotherapy but without any significant gain in overall survival. A meta-analysis based on individual data of these randomized studies has confirmed a significant impact of adjuvant chemotherapy on relapse, either local or metastatic, but without any significant benefit on survival. It should be of importance to include the last recent large trials in a new meta-analysis of source data in order to more carefully analyze a possible benefit of systemic adjuvant chemotherapy in localized sarcoma. Until this study is performed, it is an obvious conclusion that adjuvant chemotherapy has not reproducibly demonstrated its capacity to improve overall survival and relapse-free survival in an unselected population of patients. In 2011, there is therefore an urgent need to determine whether or not there are small subpopulations of patients truly benefiting from adjuvant chemotherapy (with conventional agents), and to identify prospectively these populations. With the exception of male, older than 40 years, with a non-optimal resection of their primary (R1 resection) or in the subgroup of grade 3 STS, no other relevant clinical prognostic/predictive factors have been highlighted. The take home messages in 2011 could be as follows: (1) adjuvant chemotherapy is not recommended routinely in high-grade STS; (2) adjuvant chemotherapy is recommended in patients underwent a R1 resection and with a grade 3 STS; (3) adjuvant chemotherapy cannot rescue an inadequate initial surgery; (4) if selected, chemotherapy has to be contain anthracycline and fractionated adequate dose of ifosfamide (around 9 g/m² per cycle); (5) the era of adjuvant chemotherapy trials with the same chemotherapy regimen in all histological subtype of sarcoma is ended; and (6) prognosis of patients with a localized STS starts at diagnosis. The dramatic activity of imatinib in GIST, the heterogeneous outcome of each histological subtype of sarcomas akin to being different diseases, and the high sensitivity of some histological subtypes of sarcoma to specific agents clearly open a new era in the management and the evaluation of new agents in the field of STS. The design of the future adjuvant trials has to incorporate these new findings and new prognostic/predictive biomarkers in order to improve the as yet dismal prognosis of patients developing high-grade localized STS.     

Thermochemotherapy in patients with extremity high-risk soft tissue sarcomas (HR-STS)

Purpose: We report data from phase II trials examining the efficacy of multimodality treatment with neoadjuvant chemotherapy, hyperthermia, surgery, radiation and postoperative thermochemotherapy in adult patients with high-risk sarcomas of the extremities.

Patients and methods: From 1991 to 2001 47 patients with high risk soft tissue sarcoma of the extremities were prospectively treated in two clinical trials with a treatment plan of four cycles of etoposide, ifosfamide and doxorubicin combined with regional hyperthermia followed by surgery, radiation and adjuvant chemotherapy.

Results: Objective response rate assessable in 39 patients was 21% (one complete and seven partial responses). A favourable histological response (>75% tumour necrosis) was observed in 34% of the 35 evaluable patients who had surgical resection. Median overall survival (OS) was 105 months. The five-year probability of local failure-free survival (LFFS), distant disease-free survival (DDFS), event-free survival (EFS) and OS were 48%, 55%, 35% and 57%, respectively. There were no significant differences between responders and non-responders of minimum temperatures (Tmin) and time-averaged temperatures achieved in 50% (T₅₀) and 90% (T₉₀) at all measured tumour sites. Response to this neoadjuvant regimen predicted for prolonged LFFS (p = 0.0123), but not for OS (p = 0.2). Limb preservation was achieved in 37 patients (79%) and did not result in inferior DDFS (52% versus 50%) or OS (61% versus 50%) at five years (p = 0.8) in comparison to patients who underwent amputation.

Conclusion: Response to combined modality treatment with RHT and neoadjuvant chemotherapy was predictive for an improved LFFS and led to limb preservation in 79% of patients with extremity sarcomas.