Prognostic factors for survival in soft tissue sarcoma

Between 1975 and 1984, 125 cases of histologically confirmed soft tissue sarcomata (STS) were registered in the Department of Clinical Oncology in Edinburgh. Of these, 100 were eligible for analysis of prognostic factors. The overall 5-year survival rate was 21.5%. Univariate analysis demonstrated that extent of surgery, radical versus palliative or no radiotherapy, mass as a presenting symptom, metastases at presentation, site, histological type, mitotic activity, grade and UICC stage all had a statistically significant effect on survival. Analysis using the proportional hazard regression model was performed on the 87 patients for whom all variables were recorded. When all histological and clinical features and treatment modalities were included in the model then radiotherapy, surgery, necrosis, sex and mitoses were identified as independent prognostic variables. When symptoms and treatment were excluded then the multivariate analysis identified sex and mitotic activity as independent parameters. For the 33 superficial STS with tumour size recorded multivariate analysis revealed size, necrosis and cellularity as independent prognostic variables. For the 31 deep STS histological type, sex, surgery and radiotherapy were identified as independent prognostic parameters.     

Hyperthermia in soft tissue sarcoma

Patients with high-risk soft tissue sarcomas (STS)–FNCLCC grade 2–3, size >5 cm, deep to the fascia—are at risk for developing local recurrence and distant metastasis despite surgical tumor resection. Therefore, the management of high–risk STS requires a multidisciplinary approach. Besides surgery, radiotherapy, and chemotherapy, regional hyperthermia (RHT) has the potential to become the fourth standard treatment modality for the treatment of these patients. RHT means non-invasive selective heating of the tumor area to temperatures within the range of 40–43°C for 60 min by the use of an electromagnetic heating device. Thereby RHT is always applied in addition to radiotherapy or chemotherapy or both but is not effective as a single treatment. Beside direct cytotoxicity, RHT in combination with chemotherapy enhances the drug cytotoxicity mainly by increased chemical reaction and intratumoral drug accumulation. For the neoadjuvant setting, RHT in combination with a doxorubicin- and ifosfamide-based chemotherapy has been shown to dramatically improve the tumor response rate but also prevents from early disease progression as compared to chemotherapy alone. The addition of RHT to a multimodal treatment of high-risk STS consisting of surgery, radiotherapy, and chemotherapy either in the neoadjuvant setting but also after incomplete or marginal tumor resection has been shown to significantly improve local recurrence- and disease-free survival. Based on these results and in conjunction with the low RHT-related toxicity, RHT combined with preoperative or postoperative chemotherapy should be considered as an additional standard treatment option for the multidisciplinary treatment of locally advanced high-grade STS.     

Association between aryl hydrocarbon receptor genotype and survival in soft tissue sarcoma.

PURPOSE: Accumulating evidence shows that germline polymorphisms may affect survival in cancer. The purpose of this study was to investigate the association between polymorphisms in a group of candidate genes and survival with soft tissue sarcoma. PATIENTS AND METHODS: We measured single nucleotide polymorphisms in the metabolizing, detoxifying, and DNA repair pathways in 120 newly diagnosed patients with soft tissue sarcoma. We assessed polymorphisms in the aryl hydrocarbon receptor (AhR-Arg554Lys), null variants of the glutathione S-transferase superfamily (GSTM1 and GSTT1), x-ray repair cross-complementing 1 and 3, and Xeroderma pigmentosum, group D (XRCC1-Arg399Gln, XRCC3-Thr241Met, XPD-Lys751Gln). We followed the patients for survival for a median of 7.6 years. RESULTS: Cox proportional hazards models demonstrated that a polymorphism at codon 554 in exon 10 of the AhR was significantly and adversely associated with survival (hazard ratio, 2.2; 95% CI, 1.3 to 3.9; P <.01), even while accounting for major clinical characteristics such as tumor grade, tumor size, anatomic site, and patient age. CONCLUSION: Further study of the role of the AhR polymorphism is warranted.     

Retroperitoneal soft tissue sarcoma

The objective of the current study was to define the optimal treatment for patients with retroperitoneal soft tissue sarcomas (RPS). The authors conducted a review of the pertinent literature and found that the majority of patients had locally advanced RPS at the time of diagnosis. Surgery was the mainstay of treatment, and macroscopic total excision was feasible in approximately 50-67% of patients. The 5-year probability of local control was approximately 50%, and the likelihood of developing distant metastasis was approximately 20-30%. The 5-year survival rate was approximately 50%, and deaths due to recurrent RPS continued to occur after 5 years. Postoperative radiotherapy (RT) decreased the likelihood of local recurrence, although it demonstrated no impact on survival. Adjuvant chemotherapy had no proven efficacy. The factor that was found to have the greatest impact on the prognosis for patients with RPS was the ability to achieve a macroscopic total resection. The authors concluded that RPS usually is advanced at the time of diagnosis. The optimal treatment was complete resection. Most patients experienced recurrent disease after surgery, and the most common site of failure was local. Adjuvant RT reduced the risk of local recurrence, but its impact on survival was questionable.     

Primary and recurrent retroperitoneal soft tissue sarcoma: prognostic factors affecting survival

BACKGROUND AND OBJECTIVES: To analyze treatment and survival in 34 patients (28 resected) with primary or recurrent retroperitoneal sarcoma (RPS). METHODS: Between July 1994 and January 2001, 34 patients (15M, 19F; mean age: 56 years, range: 25-77) were evaluated. Complete resection was defined as removal of gross tumor with histologically confirmed clear resection margins. RESULTS: Twenty-eight out of 34 patients (82%) (15 were affected by primary RPS, and 13 by recurrent RPS), underwent surgical exploration. Twenty-three patients had a grossly and microscopically complete resection, (3 having a grossly incomplete resection and 2 patients with a grossly complete resection having histologically involved resection margins). Twenty-one out of 28 patients (75%) underwent removal of contiguous intra-abdominal organs. Preoperative mortality was nil, and morbidity occurred in six cases only (21%). High tumor grade results a significant variable for a worse survival in all 28 patients (100% 5 years survival for low grade vs. 0% for high grade; P = 0.0004). Amongst completely resected patients, only histologic grade and peroperative blood transfusions affected disease-free survival (P = 0.04 and P = 0.05, respectively). CONCLUSIONS: An aggressive surgical approach in both primary and recurrent RPS is associated with long-term survival.     

Five-year survival after pulmonary metastasectomy for adult soft tissue sarcoma.

Determinants of 5-year survival were evaluated after complete resection of pulmonary metastases from adult soft-tissue sarcomas. Fifty-eight patients had complete resection (median survival 25 months, P = 0.0002), with a 25.8% absolute 5-year survival (15 of 58 patients); six patients had unresectable disease (median survival 6 months) and were excluded from additional analysis. Eleven patients remain disease free, with a median follow-up of 76 months. Significant independent prognostic indicators associated with improved survival (P less than 0.05) included metastasis doubling time of 40 days or greater (median survival 37 months versus 15 months if less than 40 days); unilateral disease on preoperative radiography (33 months versus 15 months if bilateral disease); three or fewer nodules on preoperative computed tomography (40 months versus 14 months if 4 or more nodules); two nodules or fewer resected (40 months versus 17 months if 3 or more nodules resected), and tumor histology (33 months for malignant fibrous histiocytoma versus 17 months for all others). Multivariate analysis identified the number of nodules detected by computed tomography preoperatively as having significant prognostic value.     

Rhabdomyosarcoma and soft tissue sarcoma in childhood

The past year has seen a greater understanding of the means by which the alveolar rhabdomyosarcoma gene fusions (PAX-FKHR) lead to the malignant phenotype. The treatment of the primary tumor in rhabdomyosarcoma has been reexamined, with the roles of surgery and radiation expanding in American studies and decreasing in European ones. "Megatherapy" approaches with stem cell or bone marrow autologous transplants still have not found a role in the treatment of metastatic rhabdomyosarcoma. Our understanding of the natural history of nonrhabdo soft tissue sarcomas in children has increased, and molecular diagnosis is becoming established. The role of chemotherapy in treatment remains controversial.     

Impact of improved local control on survival in patients with soft tissue sarcoma

An estimate has been made of the gain in survival if the local failure rate for sarcoma of soft tissue was reduced to zero by the application of new treatment methods. The assumption is that the loss, due to distant metastasis and intercurrent disease among patients who achieve local control by the current treatment, would be the same among new local controls. For patients with stage M0 disease at diagnosis (all sites, all histological types), the current local failure rate is approximately 30%. By eliminating these failures, the overall survival rate would be expected to increase by 10-20 percentage points.     

Effect of marital status on treatment and survival of extremity soft tissue sarcoma

BackgroundSpousal support has been hypothesized as providing important psychosocial support for patients and as such has been noted to provide a survival advantage in a number of chronic diseases and cancers. However, the specific effect of marital status on survival in soft tissue sarcomas (STSs) of the extremity has not been explored in detail.Patients and methodsA total of 7384 patients were evaluated for this study using a Surveillance, Epidemiology, and End Results (SEER) registry query for patients over 20 years old with extremity STS diagnosed between 2004 and 2009. Survival outcomes were analyzed using Gray's test after patients were stratified by marital status. The Fine and Gray model, a multivariable regression model, was used to assess whether marital status was an independent predictor of sarcoma specific death. Statistical significance was maintained at P < 0.05.ResultsAnalysis of the SEER database showed that single patients were more likely to die of their STS and at a faster rate than married patients. No differences were noted in tumor size and tumor site on presentation between married and single patients. However, single patients presented with higher grade tumors more frequently (P = 0.013), received less radiotherapy (P < 0.001), and had less surgery carried out (P < 0.001), compared with their married peers. Regression analysis showed that after accounting for tumor size, grade, site, histology, use of radiotherapy, age, gender, region where the patients were from, and income, being single continued to serve as an independent predictor of sarcoma-specific death; P < 0.0001.ConclusionOverall survival is worse for single patients, when compared with married patients, with STS. Single patients do not undergo surgical resection or receive radiation therapy as frequently as their married counterparts. Social support systems and barriers to care should be evaluated at time of diagnosis and addressed in single patients to potentially improve survival outcomes.     

Modern pathological evaluation of soft tissue sarcoma specimens and its potential role in soft tissue sarcoma research

Opinion statement The vast majority of soft tissue tumors (STT), especially sarcomas, should be examined according to a national standard for pathologic evaluation, including a national consensus on a grading system and elements of a synoptic pathology report. The margins should be separated into fascial margins and other surgically cut margins. If questions about the diagnosis arise, a second opinion should be sought from an expert in sarcoma pathology. Whenever possible, tissue should be frozen for potential molecular diagnosis and additional tissue banked for research. Finally, there is a need for a national registry for rare sarcoma types.     

Factors associated with actual long-term survival following soft tissue sarcoma pulmonary metastasectomy

Aims

To identify clinicopathologic and treatment variables associated with long-term overall survival (OS) in soft tissue sarcoma (STS) patients with lung metastases undergoing pulmonary metastasectomy (PM).

Methods

Retrospective review of 94 STS PM patients with an actual follow-up ≥5 years. Data were collected on demographics, tumor features, treatment, and outcome.

Results

Most primary tumors were intermediate/high grade and the common histopathologies were evenly distributed. Half of the primary tumors were located on the extremities. The mean disease-free interval (DFI) from time of original diagnosis until metastases was 25 months (median 15 months). Eighteen patients had synchronous metastatic disease. Bilateral pulmonary metastases and >1 metastasis were common. The median number of metastases resected was 2.5. Thirty-four patients had extrapulmonary tumor at the time of PM; all extrapulmonary disease was resected. Negative margin resection (R0) PM was performed in 74 patients. Actual 5-year disease-free survival (DFS) and OS for all patients were 5% and 15%, respectively. For the R0 group, actual 5-year DFS and OS were 7% and 18%, respectively. R0 resection and a prolonged DFI were associated with improved OS. Patient characteristics, tumor features, local recurrence, and adjuvant therapy did not affect OS.

Conclusions

Less than 20% of STS PM patients will survive 5 years. Complete resection and DFI are the most predictive factors for prolonged survival.     

Localized extremity soft tissue sarcoma: an analysis of factors affecting survival

The management of extremity soft tissue sarcoma is undergoing rapid change as new techniques of adjuvant treatment are developed. Critical assessment of these advances requires a fundamental understanding of the natural course of this disease. In an effort to define important prognostic factors, this review of 423 adults with localized extremity soft tissue sarcomas, treated at one institution (1968 to 1978), was undertaken. The effect of the following variables on survival was examined: patient factors, ie, age, sex, symptoms, and status at presentation; tumor factors, ie, site, size, depth, bone or neurovascular invasion, histogenesis, grade, and nodal status; and treatment factors, ie, biopsy technique, type of operation, surgical margins, adjuvant treatment, and subsequent local treatment failure. Patient factors with an adverse impact on survival included age greater than 53 and the presence of local symptoms. High tumor grade, positive regional nodes, histology other than liposarcoma, fibrosarcoma or malignant fibrohistiocytoma, invasion of vital structures, proximal site, deep location, and size greater than 10 cm were also poor prognosticators. Treatment factors correlating with optimal survival included limb sparing surgery, adequate margins, biopsy with delayed definitive resection, and absence of subsequent local failure. Patients treated by amputation had a greater proportion of risk factors than patients treated with limb-sparing surgery (LSS). When the data were subjected to multivariate analysis, the following variables emerged as independent predictors of poor outcome: local symptoms, age greater than 53, high grade, proximal site, size greater than 10 cm, positive regional nodes, surgery by amputation, and inadequate margins. These factors are now to be evaluated in our prospective study based on 600 patients with soft tissue sarcoma of all sites admitted to our institution in the last 3 years. These factors should be considered as important stratifications in prospective trials.     

Pathology of soft tissue sarcoma

The evaluation and treatment of soft tissue sarcomas has never been more demanding than it is today. The pathologist plays a central role in this process and is an integral member of the multidisciplinary sarcoma treatment team. This article provides a brief summary of the role of the soft tissue pathologist and includes sections on methods of diagnosis, frozen section, classification of sarcomas, expert consultation, molecular pathology, grading, assessment of treatment response, and tumor banking.     

软组织肉瘤的放射治疗

软组织肉瘤(soft tissue sarcomas,STS) 是起源于结缔组织的软组织恶性肿瘤,具有多种不同类型。手术是 STS 主要治疗方法,放疗也是其重要的治疗方式并且是综合治疗早期选择之一。对 STS 进行放疗已经超过 50 年历史,术前和术后放疗对于局部控制都有疗效,只是不良反应不同。软组织肉瘤放疗技术包括远距离放疗(适形放疗、调强放疗、立体定向放疗等) 、近距离放疗(组织间插植放疗、腔内后装放疗、术中放疗等) 等。放疗技术的进步,提高了放疗的精准性和确定性,降低了对病灶周围正常组织的损伤。本文主要针对 STS 放疗技术以及适用原则进行综述。      

软组织肉瘤的放射治疗

放疗是软组织肉瘤重要治疗手段之一,术前或术后放疗可降低肿瘤局部复发风险,局部扩大切除结合术前或术后放疗能达到与截肢术同等的长期生存率并且保存肢体功能,近些年来随着放疗技术的进步,软组织肉瘤放疗的正常组织损伤风险正在减少。     

Screening populations at high risk for soft tissue sarcoma and surveillance following soft tissue sarcoma resection

Soft tissue sarcomas (STS) are a rare and diverse group of tumors that affect both adult and pediatric populations. This review discusses current screening recommendations for populations at increased risk for STS, including those with genetic predispositions. We also review surveillance guidelines for those at risk for recurrence following curative-intent surgery.