Gemcitabine in the treatment of soft tissue sarcomas

Soft tissue sarcomas (STS) are rare mesenchymal tumors with poor prognosis once they present as advanced or metastasized disease. Only few cytostatic drugs have been proven to be active in sarcoma patients and there is a clear need for further treatment options in patients with tumors refractory to standard chemotherapy. Gemcitabine, a nucleoside analogue, has shown activity in several epithelial tumors. Clinical data on the activity of gemcitabine in STS, however, are scarce and heterogeneous. In trials including all subtypes of sarcomas response rates observed with single and multiagent schedules are ranging from 3 to 53%. Histopathological subtypes which seem to exhibit an increased susceptibility to gemcitabine are uterine leiomyosarcomas and angiosarcomas. The synergistic role of other cytostatic drugs, e.g. the role of taxanes, still remains unclear and warrants further trials. We here review the available literature on gemcitabine in the treatment of STS.     

Delay in diagnosis of soft tissue sarcomas.

AIM: We reviewed 100 patients referred with soft tissue sarcoma between May 1999 to determine doctor- and patient-related delay. METHODS: Patient delay is defined as longer than one month from first symptoms till doctor's visit, doctor delay as longer than one month from first visit till definitive diagnosis. Sixty-eight patients had a multifactional delay. RESULTS: Forty-seven patients showed patient delay, with a median patient delay of 4 months, ranging from 2 to 240 months. The main reason for this delay is a painless mass that is mostly ignored. When pain is present, median patient delay is shorter.Twenty-seven patients experienced doctor delay, ranging from 2 to 79 months, with a median of 6 months. The most frequent reason was a misdiagnosis from the outset, on a clinical basis only, or due to a wrong diagnosis on ultrasound. Only two of these 27 patients had a biopsy, showing a benign tumour.High grade tumours are diagnosed earlier, 85% within 6 months. CONCLUSIONS: Delay in diagnosis of soft tissue sarcomas is still a problem requiring better patient and doctor education.     

屏障切除术治疗软组织肉瘤

软组织肉瘤以手术切除为首选的治疗原则是国内外的共识。切除的方法主要以距肉瘤的远近来确定切缘,然而距离肉瘤多少厘米进行切除尚未有统一的标准,使临床实践无所遵循。屏障切除术摈弃了切缘距离的理论,选择有阻挡肉瘤生长的屏障组织作为设计切缘的依据,使得术前设计和术中解剖看得见、摸得着。由于是屏障性切缘,因而复发率明显下降。将屏障切除和修复重建结合,即降低了复发率又恢复了功能,相得益彰。     

Fast neutrons in the treatment of soft tissue sarcomas

Results of treatment of 101 cases of soft tissue sarcoma are presented in the paper. Preoperative irradiation technique and radical program of treatment are described. Combined radiation and surgical treatment was given to 45 patients whereas conservative--to 56. Sixty-three cases received adjuvant combination chemotherapy. Response and three-year survival rates were compared to those in control group treated by photons. The results observed in patients of combined and conservative treatment groups who had been irradiated with fast neutrons proved significantly better than in controls. These data suggest vistas in application of fast neutron irradiation for the treatment of soft tissue sarcomas.     

Antiangiogenesis agents in the treatment of soft tissue sarcomas

Soft tissue sarcomas (STSs) are a heterogeneous group of malignancies that includes >50 different subtypes, each with unique clinical and pathologic qualities. In general, there is a 50% cure rate, and most cures are achieved with complete surgical resection with or without radiation therapy. The results from chemotherapeutic agents for unresectable or metastatic disease have been disappointing with minimal long‐term benefit. New targeted and novel agents are needed to improve response and survival. Tumor angiogenesis has been an intense focus in cancer therapy over the past decade. Several of numerous antiangiogenesis agents have been developed, and many already have been approved for the treatment of both solid and liquid tumors. Certain STSs are highly vascular tumors that often demonstrate angiogenesis markers. The objective of this review was to evaluate these angiogenesis markers in defining the role of angiogenesis in the treatment of patients with STS. In addition, the authors conducted an in‐depth review of the results from using key antiangiogenesis agents in the treatment of STS. Cancer 2010. © 2010 American Cancer Society.     

Intraarterial adriamycin in the treatment of soft tissue sarcomas

Ten patients with extremity sarcomas adriamycin 60 mg/M² into the artery supp supplying the area of tumor. There were minimal local side effects consisting of occasional local erythema or slight transitory pain. Nine of these patients had subsequent surgery, and an average 32.86% histologic tumor necrosis was recorded in the peripherally viable areas of seven patients with residual tumor, compared to a 5.71 % necrosis recorded in the biopsy sections (P value < 0.01).     

Direct angioscintigraphy of soft tissue sarcomas in outpatient diagnosis

Direct angioscintigraphy was carried out in 80 patients suspected for soft-tissue tumors in the extremities. Relevant procedure, predictive value of the diagnostic test, relationship between scintigraphic patterns and those of tumor histology as well as factors adversely affecting examination results are discussed. The method was shown to be sufficiently accurate (0.79) and may find effective application in examination of outpatients.     

腺泡状软组织肉瘤的临床治疗分析

目的探讨腺泡状软组织肉瘤手术切除及辅助放、化疗的临床治疗效果。方法对1993～2006年间收治的腺泡状软组织肉瘤12例回顾性分析。男5例,女7例。年龄11～37岁。肿瘤直径平均5.5cm。结果12例手术后切除缘评价中,达到广泛切除缘者10例,边缘切除缘者2例,术后辅助放疗2例,全组均予辅助化疗。12例手术后复发3例,占25%。有7例发生转移,首诊时转移2例,其中肺转移瘤5例,脑转移瘤2例。转移率58.3%。转移瘤单纯化疗5例中PR3例,NC1例,PD1例,3例PR患者均采用MAI方案。随访时间10个月～10年6个月,12例中7例生存,5例死亡,经过Kaolan-Meire生存率计算,3年生存率81.2%,5年生存率52.8%。结论腺泡状软组织肉瘤外科治疗应以广泛切除术为基本原则,术后辅助放疗可以减少复发,辅助化疗是转移瘤的主要治疗方法。     

Centralised treatment of soft tissue sarcomas in adults

The clinical research developed in specialised centres and oncologic cooperative groups has permitted various scientific societies to collect recommendations used in the treatment of soft tissue sarcomas (STS) and incorporate them into clinical practice guidelines (CPG). Some studies have been conducted in diverse healthcare ambits to assess the influence of CPG. This revision of the medical literature analyses the impact that healthcare management -centralised or otherwise- and clinical practice in conformity with CPG have on the clinical outcome variables of STS. Eight CPG have been identified, as well as 12 conformity studies or audits. These conformity studies and audits demonstrate that the grade of adaptation of medical interventions with CPG, medical healthcare in reference centres and procedures of referrals to these centres, as well as the process of organising healthcare teams into Sarcoma Committees, have a significant influence on clinical outcome. We can conclude that excellent healthcare of STS implies the adaptation of healthcare practice to CPG, the existence of Reference Centres guided by Sarcoma Committees, and the observance of strict referral procedures within the Healthcare Area.     

Surgical aspects in the treatment of retroperitoneal soft tissue sarcomas

Abdominal soft tissue sarcomas (ASTS) represent a rare malignancy of the abdomen. Diagnosis is often delayed because ASTS tend to be asymptomatic for a long time. Typical clinical symptoms such as pain and augmentation of the abdominal girth develop as a result of the compressing and displacing rather than infiltrating growth pattern of large ASTS. Treatment of patients with ASTS should be managed interdisciplinarily in a tumourboard. Surgery (i.e. wide excision with negative margins) represents the only potentially curative treatment option. Multimodal treatment with radiotherapy and/or chemotherapy, however, is indispensable to reduce the rather high local recurrence rate in these patients despite complete resection. A preoperative core needle biopsy is recommended if diagnosis and hence also therapy are unclear: the biopsy pathway should be chosen in accordance with the surgeon, and the excision has to be performed afterwards within primary surgery. The aggressiveness of surgery is still under debate and ranges from a tissue/organ-sparing approach to an extensive approach with compartmental resection. Thus, the oncologic surgeon must be able to handle complex multivisceral resection as well as extensive vascular reconstruction. Surgery for local recurrence has been shown to be feasible, and the presence of distant metastases usually represents a contraindication for surgery.     

Postoperative radiotherapy in the treatment of extremity soft tissue sarcomas

From 1966 to 1983, 50 patients with extremity soft tissue sarcomas were treated with wide local excision and postoperative radiotherapy at the Mallinckrodt Institute of Radiology. The median follow-up was 70 months (range 28 to 168). Grade was the most significant factor affecting survival: all 11 patients with well differentiated tumor survived versus 6/8 patients with moderate and 17/31 patients with poorly differentiated tumors (p less than 0.01). In addition, lymph node involvement at diagnosis conferred a worse prognosis with only 2/5 patients alive after treatment (p less than 0.05). Eleven of 50 (22%) failed locally. Factors affecting local control included gross residual tumor after operation and limited treatment volume. Among the 35 patients who did not have gross residual tumor or limited treatment volume, two patients who received less than 5000 cGy failed locally versus 1/18 patients who received between 5000-6000 cGy and 2/15 patients who received more than 6000 cGy. Microscopically positive margins and a volume encompassing less than the total muscular compartment was not associated with an increase in the incidence of local failure. Eight patients developed local complication: five due to retreatment for local recurrence. Overall, 24/26 patients who are alive have had their limbs preserved with normal function.     

Concepts in limb-sparing treatment of adult soft tissue sarcomas

Pretreatment assessment of patients with soft tissue sarcomas of the extremities requires careful attention to a biopsy approach that will establish the precise diagnosis and will not compromise the subsequent definitive operative procedure. Also, staging procedures are required to evaluate the status of both local and distant sites. Limb-sparing surgery for high grade extremity soft tissue sarcomas is a feasible and appropriate approach in approximately 90% of patients with such lesions. Wide gross surgical margins around the sarcoma are the optimal operative approach. Circumstantial evidence is convincing that local treatment failure can be reduced by adjuvant regional radiation treatment when surgical margins are narrow, and end results appear to be equal to those obtained by more extensive surgical resection alone. Adjuvant radiation following operation with optimal gross surgical margins has not been established as adding benefit. Although some groups treating soft tissue sarcomas do use intraarterial chemotherapy in conjunction with these other modalities, there is, as yet, no convincing evidence that this aspect of the multimodality treatment adds to local and/or systemic disease control. The efficacy of adjuvant systemic chemotherapy for high grade soft tissue sarcomas remains to be established within the context of prospective clinical trials.     

肢体骨和软组织肉瘤的化疗进展(一)

骨和软组织肉瘤的临床表现和组织学表现多种多样,其发病率比较低。在20世纪70年代之前,手术是治疗四肢软组织肉瘤和骨肉瘤的主要方法。但是单纯手术治疗,患者术后的局部复发率很高。即使局部肿瘤得到控制,仍然有50%以上的软组织肉瘤患者和80%的骨肉瘤(主要是成骨肉瘤和尤文肉瘤)患者,在     

Pediatric soft tissue sarcomas

Many of the soft tissue sarcomas that occur in children are of the same histology as those in adults; however, the relative prevalence of these sarcomas is different between children and adults. In some cases, the biologic behavior of pediatric sarcomas is more benign than that in adults. Treatment for sarcomas in children is also different. Pediatric sarcomas are more commonly responsive to chemotherapy. Furthermore, in children who are still growing, surgery and radiation are associated with higher morbidity than in adults. This article discusses the diagnosis and treatment of rhabdomyosarcoma and undifferentiated sarcomas, with an emphasis on surgical considerations, and the diagnosis and treatment of nonrhabdomyosarcomatous soft tissue sarcomas in children.     

Pelvic soft tissue sarcomas

Pelvic soft tissue sarcomas (PSTS) are a rare, heterogeneous group of tumors. They have been usually analyzed with retroperitoneal sarcomas (RPS), but actually have key differences. Due to their unique anatomic location, symptomatic presentation of PSTS may be more common than RPS. Adequate imaging approach is paramount for guiding differential diagnosis, while preoperative biopsy is mandatory, especially when preoperative treatment may be considered as initial approach. The most frequent histologic subtype is leiomyosarcoma, which is different as expected in the retroperitoneum where liposarcoma is the commonest histology. Also solitary fibrous tumor is commonly diagnosed in the pelvis. Surgical approach for PSTS differs from that for RPS mainly due to anatomic relations. Similarly, in the lack of definite evidence from specific trials about neoadjuvant and adjuvant treatments, the anatomic constraints to obtain wide margins in the pelvis as well as the expected functional outcome in case of organ resections should be factored into decision for individualized treatment offer. Vascular and genitourinary involvement are frequent, as well as herniation through pelvic foramina. For these reasons a multidisciplinary surgical team should always be considered. Early referral of these patients to high-volume centers is critical and may impact on survival, given that optimal initial resection is a major predictor of curative treatment. International consensus on PSTS treatment is advocated, similarly to the recent efforts realized for RPS.     

The role of neutrons in the treatment of soft tissue sarcomas

Two-hundred twenty-one patients with soft tissue sarcoma were treated from 1978 to 1983. Treatment was nonrandomized and consisted of neutron irradiation in 94 cases with gross tumor. Treatment was nonrandomized and consisted of neutron boost irradiation after photon-irradiation or electron-irradiation in 127 cases with no gross tumor after surgery. Patient distribution according to UICC (1978) criteria was 15, 100, and 106 of T1, T2, and T3 respectively. Distribution by pathologic grade was 54, 107, and 60 for Grade 1, Grade 2, and Grade 3 tumors. Distribution by tumor residuum after surgery was 23 cases without microscopic disease (R0), 104 with microscopic disease (R1), and 94 with gross residuum (R2) or nonoperative disease. Five-year follow-up reveals a significant difference (P = 0.024) in disease-free survival (DFS) for T1 (60%), T2 (71%), and T3 (29%, P = 0.016) tumors. Similarly, there are significant DFS differences among G 1 (74%), G 2 (48%, P = 0.035), and G 3 lesions (22%, P = 0.024). The impact of tumor bulk or residuum on DFS after operation is significant when comparing R0 (87%) and R1 (65%) disease (P = 0.042). The 5-year survival of patients who had gross residuum (R2) after surgery was significantly worse (26%, P = 0.003). Ninety percent of patients failed treatment locally and distally within 2 years. The late morbidity rate was 27% for neutron and 7% for neutron-boost irradiation. In our series and reported photon data, local control rates for tumors 5 to 10 cm with neutrons were 76% and 53%, respectively. Low energy (d(14) + Be) neutrons are considered beneficial in the postoperative treatment of well-differentiated soft tissue sarcomas where gross tumor remains. Neutron-boost irradiation is of potential benefit in the treatment after operation of T2-3, and G 1-2 tumors if there is microscopic residual tumor.