Dynamic prediction of overall survival for patients with high-grade extremity soft tissue sarcoma

Purpose

There is increasing interest in personalized prediction of disease progression for soft tissue sarcoma patients. Currently, available prediction models are limited to predictions from time of surgery or diagnosis. This study updates predictions of overall survival at different times during follow-up by using the concept of dynamic prediction.

Flap reconstruction does not increase complication rates following surgical resection of extremity soft tissue sarcoma

Background

Flap reconstruction plays an essential role in the surgical management of extremity soft tissue sarcoma (ESTS) for many patients. But flaps increase the duration and complexity of the surgery and their contribution to overall morbidity is unclear. This study directly compares the complication rates in patients with ESTS undergoing either flap reconstruction or primary wound closure and explores contributing factors.

Preoperative radiotherapy for soft tissue sarcoma: The Peter MacCallum Cancer Centre experience

AIM: Radiotherapy has been shown to improve local control in combination with limb-sparing or conservative surgery in the management of localised soft tissue sarcoma. Our centre's treatment protocol is to offer preoperative external beam radiotherapy (50.4Gy in 28 fractions) followed by surgery four to six weeks later. The aim of this study is to review the treatment outcome and toxicity of patients treated with this protocol. METHODS: Consecutive patients with localised extremity or truncal soft tissue sarcoma who presented between January 1996 and December 2000 and treated with preoperative radiotherapy followed by limb-sparing surgery were reviewed. Patients with recurrent disease or metastatic disease at diagnosis and patients below the age of 16years were excluded. Local and distant recurrence, overall survival and treatment toxicity were analyzed. RESULTS: Sixty-seven cases were identified (41 males and 26 females). The median age was 52years (range 17 to 82). The majority (79%) had tumours located in the lower limb. The most common histological diagnoses were malignant fibrous histiocytoma and liposarcoma. The median follow-up was 4.1years (range 0.6 to 6.9). There were six local recurrences, two of which were successfully salvaged. Twenty patients developed distant metastases. The estimated 5-year actuarial local recurrence free, distant recurrence free and overall survival were 93%, 68% and 73% respectively. Acute radiotherapy toxicity and wound complications were acceptable and late toxicity was uncommon. CONCLUSION: Preoperative radiotherapy followed by surgery provides effective local control in the management of soft tissue sarcoma.     

MRI surveillance for local recurrence in extremity soft tissue sarcoma

IntroductionThe role of MRI in surveillance for local recurrence (LR) remains uncertain in extremity soft tissue sarcoma (STS). The aims of this study were 1) to examine the usefulness of MRI in detecting LR, 2) to identify the characteristics of LR detected by MRI, and 3) to examine whether MRI surveillance is associated with oncologic outcome.Materials and Methods477 patients who had regular surveillance for LR after surgery for extremity STS were reviewed. Surveillance was performed by routine MRI in 325 patients or other imaging modalities in 152 patients.ResultsThe rate of MRI-detected LR, defined as clinically undetectable LR identified on MRI, was 10.5% in the MRI surveillance cohort. The detection rates of MRI-detected LR were significantly higher in the patients with high risk of LR. MRI-detected LRs were more commonly located in the thigh or buttock (p = 0.005), were smaller (p = 0.001) and had LRs without mass formation (p = 0.007) than non-MRI-detected LRs. On Kaplan-Meier analysis, patients with MRI-detected LR tended to have better post-LR survival (p = 0.104).ConclusionRoutine MRI surveillance can detect a significant number of clinically undetectable LRs in extremity STS especially for LRs in the thigh or buttock, small LRs or LRs without mass formation.     

术前放疗在软组织肉瘤保肢手术中的临床应用

目的 探讨术前放疗在软组织肉瘤保肢手术中的临床效果.方法 本组男17例,女13例;首诊6例,复发24例;年龄最大89岁,最小11岁,平均44.5岁.术前经病理检查确诊后接受直线加速器外照射,DT50Gy/25次/35天,放疗结束后休息2-4周即接受手术治疗.结果 随访时间:术后12-106个月,中位随访时间:48.3个月.术前放疗后肿瘤达到CR (complete remission) 2例、PR (partial remission) 25例,2例无变化,1例继续增大.术后因肺转移死亡6例(局部均无复发),占20% (6/30),其中2例为治疗期间出现肺转移,3例术后1年内出现肺转移,1例术后5年出现肺转移.2例分别于术后15个月和73个月局部复发,其中前者经二次广泛切除肿瘤后无复发及转移,后者合并病理性骨折而行截肢.28例无局部复发及远处转移,局部控制率93.3%(28/30).8例伤口延迟愈合,占28.7% (8/30).结论 术前放疗可以降低软组织肉瘤外科分期,缩小外科切除边界,最大限度保留肢体功能,降低局部复发率,降低保肢风险.     

Post-metastasis survival in extremity soft tissue sarcoma: A recursive partitioning analysis of prognostic factors

BackgroundRecursive partitioning analysis (RPA) enables grouping of patients into homogeneous prognostic groups in a visually intuitive form and has the capacity to account for complex interactions among prognostic variables. In this study, we employed RPA to generate a prognostic model for extremity soft tissue sarcoma (STS) patients with metastatic disease.MethodsA retrospective review was conducted on 135 patients with metastatic STS who had undergone surgical removal of their primary tumours. Patient and tumour variables along with the performance of metastasectomy were analysed for possible prognostic effect on post-metastatic survival. Significant prognostic factors on multivariate analysis were incorporated into RPA to build regression trees for the prediction of post-metastatic survival.ResultsRPA identified six terminal nodes based on histological grade, performance of metastasectomy and disease-free interval (DFI). Based on the median survival time of the terminal nodes, four prognostic groups with significantly different post-metastatic survival were generated: (1) group A: low grade/metastasectomy; (2) group B: low grade/no metastasectomy/DFI ⩾ 12 months or high grade/metastasectomy; (3) group C: low grade/no metastasectomy/DFI < 12 months or high grade/no metastasectomy/DFI ⩾ 12 months; and (4) group D: high grade/no metastasectomy/DFI < 12 months. The 3-year survival rates for each group were: group A, 76.1 ± 9.6%; group B, 42.3 ± 10.3%; group C, 18.8 ± 8.0%; and group D, 0.0 ± 0.0%.ConclusionOur prognostic model using RPA successfully divides STS patients with metastasis into groups that can be easily implemented using standard clinical parameters.     

Radiotherapy to improve local control regardless of surgical margin and malignancy grade in extremity and trunk wall soft tissue sarcoma: a Scandinavian sarcoma group study

PURPOSE: Adjuvant radiotherapy has during the past decades become increasingly used in the treatment of localized soft tissue sarcoma. We evaluated the effect of radiotherapy (RT) on local recurrence rates (LRRs) in Scandinavia between 1986 and 2005. METHODS AND MATERIALS: A total of 1,093 adult patients with extremity or trunk wall soft tissue sarcoma treated at four Scandinavian sarcoma centers were stratified according to the treatment period (1986-1991, 1992-1997, and 1998-2005). The use of adjuvant RT, quality of the surgical margin, interval between surgery and RT, and LRR were analyzed. The median follow-up was 5 years. RESULTS: The use of RT (77% treated postoperatively) increased from 28% to 53%, and the 5-year LRR decreased from 27% to 15%. The rate of wide surgical margins did not increase. The risk factors for local recurrence were histologic high-grade malignancy (hazard ratio [HR], 5), an intralesional (HR, 6) or marginal (HR, 3) surgical margin, and no RT (HR, 3). The effect of RT on the LRR was also significant after a wide margin resection and in low-grade malignant tumors. The LRR was the same after preoperative and postoperative RT. The median interval from surgery to the start of RT was 7 weeks, and 98% started RT within 4 months. The LRR was the same in patients who started treatment before and after 7 weeks. CONCLUSION: The results of our study have shown that adjuvant RT effectively prevents local recurrence in soft tissue sarcoma, irrespective of the tumor depth, malignancy grade, and surgical margin status. The effect was most pronounced in deep-seated, high-grade tumors, even when removed with a wide surgical margin.     

介入性新辅助化疗在软组织肉瘤保肢治疗中的作用

目的：探讨对发生于肢体的软组织肉瘤晚期病例如何提高疗效、降低截肢率的治疗方法。方法：我们对１１例已累及血管、神经干的患者进行了以介入性新辅助化疗为主的保存肢体治疗的尝试，即：采用术前介入性新辅助化疗＋热疗－手术切除－术后内照射（辅加外照射）－化疗的综合治疗。结果：治疗后，全数患者获保存肢体，经随访２个月～３年６个月，５例无瘤生存至今，提示近期疗效满意。结论：为保存肢体而实施的介入性新辅助化疗有其合     

Contemporary role of amputation for patients with extremity soft tissue sarcoma

Introductionlimb-sparing surgery is the mainstream treatment for primary extremity soft tissue sarcoma (ESTS) at referral centers, following advances in surgical reconstructions and multimodal management. However, amputation is still needed in selected patients and has not yet been described for a ESTS cohort in a contemporary scenario.Material and methodsconsecutive patients who underwent surgery for primary ESTS from 2006 to 2018 were extracted from a prospectively collected database at our reference center. Patients receiving amputation for either primary tumor or local recurrence (LR) after limb-sparing surgery were selected for analysis.ResultsAmong 1628 primary ESTS, 29 patients underwent primary amputation (1.8%), 22/1159 (1.9%) for upper limb and 7/469 (1.5%) for lower limb ESTS. Patients were mainly affected by grade III FNCLCC (89.6%) of notable dimension (median size 16 cm, IQR 10–24). 65.5% of patients received preoperative treatments (systemic or regional chemotherapy, radiotherapy or chemo-radiation). Secondary amputation for LR was performed after a median of 23 months in 16/1599 patients (1%). Median survival time was 16.2 and 29.6 months after primary or secondary amputation respectively. Factors prompting the need for a primary amputation were most often a combination of multifocal disease, bone invasion and pain or neurovascular bundle involvement and relevant comorbidities, mainly for grade III tumors in elderly patients.ConclusionContemporary rate of amputation for ESTS at a reference center is extremely low. Still, amputation is required in selected cases with advanced presentations, especially in elderly, frail patients.     

前后侧联合入路切除大腿巨大软组织肉瘤

目的介绍经前后侧联合入路并结扎股深动脉切除大腿巨大软组织肉瘤的经验。方法对初发或复发的8例大腿巨大软组织肉瘤术前常规行MRI和DSA检查，采用经前后侧联合入路并结扎股深动脉行肿瘤广泛切除术，其中1例行术前化疗及术后放疗，3例行术后放疗，3例术后局部复发再次行广泛切除术后放疗，1例术前术后均无辅助治疗。结果8例中2例术后出现切口边缘皮肤坏死，1例经换药治愈，1例行局部推移皮瓣术后治愈。8例术后随访2～6年，4例无瘤正常生存，3例1～2年内局部复发再次行广泛切除术，术后无瘤正常生存，1例无任何辅助治疗者术后多次局部复发行姑息性局部切除术，6年后因全身衰竭死亡。结论对初发或复发的大腿巨大软组织肉瘤术前常规行MRI和DSA检查评估其局部切除的可行性，采用经前后侧联合入路并结扎股深动脉行肿瘤广泛切除术，术后辅助放疗，是较好的保肢治疗方法。术后局部复发是较常见的并发症，再次行复发灶广泛切除术及术后放疗仍可取得较好的疗效。     

Oncological outcome of patients with deeply located soft tissue sarcoma of the pelvis: A follow up study at minimum 5 years after diagnosis

Aims

The treatment of pelvic soft tissue sarcomas (STS) presents one of the most challenging problems in musculoskeletal oncology because of the complex anatomy of the pelvis, late diagnosis and large tumor size. Our study was designed to determine the outcome and prognostic factors for survival and local recurrence in patients with pelvic STS located deep to the fascia and deemed suitable for curative surgical treatment.

Patients and methods

Ninety consecutive pelvic STS patients with at least 5-year possible follow-up from diagnosis were studied. Mean age at diagnosis was 54 years. Mean follow-up and tumor size were 69 months and 13 cm, respectively. Histological grades were grade 3 in 51, grade 2 in 22 and grade 1 in 17 patients. Tumor locations were extra-pelvic or outside pelvic brim (n = 67), intra-pelvic or within pelvic brim (n = 10), and combined or involving both outside and within pelvic brim (n = 13).

Result

Surgical treatment was excision in 84 patients and hindquarter amputation in 6 patients. In 84 patients who underwent excision, surgical margin was wide in 21 patients, marginal in 33, and intralesional in 30. Radiotherapy was used for all high grade tumors. Disease-specific survival was 53.3% at 5 years. Local recurrence occurred in 23%. Development of local recurrence was related to surgical margin (p = 0.03). Local recurrence, tumor histological grade and metastasis at diagnosis independently influenced disease-specific survival (p = 0.0008, p < 0.0001, p = 0.02, respectively).

Conclusion

The patients with high grade tumors and positive surgical margins represent a particular group with high risk of local recurrence even with radiotherapy.     

Prospective evaluation of quality of surgery in soft tissue sarcoma

BACKGROUND: Prospective application of the French Sarcoma Group (FSG) method of surgery reporting in soft tissue sarcoma (STS) in a single centre. METHODS: Patients with primary STS of the extremities or trunk wall consecutively operated at the same institution from January 1996 to December 2002 were evaluated for local recurrence (LR). There were 205 patients, with AJCC/UICC stages III and IV in 51% of cases. Resection types according to FSG were R0 in 147, R1 in 53 and R2 in five cases. Radiotherapy was delivered in 163 patients and chemotherapy in 103. Multivariate analysis was performed. Overall five-year survival was 75%. Median follow-up for surviving patients was 53 months. RESULTS: Actuarial five-year LR incidence was 13% in 200 patients with gross resection (R0+R1), it was 7% in R0 and 30% in R1 patients (p<0.0001). At univariate analysis, significant prognosticators for LR were age, histotype, tumour invasion, grade and resection type R. At multivariate analysis, resection R1 (relative risk (RR) 4.3, p=0.001) and grade 3 (RR 3.9, p=0.013) independently predicted LR. Combining these two variables produced three prognostic groups for LR: group 0 (no factor, n=70), group 1 (one factor, n=94) and group 2 (two factors, n=36) with five-year LR of 4%, 12% and 39%, respectively (p=6.4x10(-7)). CONCLUSION: This first prospective evaluation of surgery reporting in STS evidences a fourfold, highly discriminating difference in LR between resections R0 and R1.     

Intensity modulated radiation therapy for primary soft tissue sarcoma of the extremity: preliminary results

PURPOSE: To report preliminary results on using intensity modulated radiation therapy (IMRT) as an adjuvant treatment in primary soft tissue sarcoma (STS) of the extremity. METHODS AND MATERIALS: Between February 2002 and March 2005, 31 adult patients with primary STS of the extremity were treated with surgery and adjuvant IMRT. Tumor size was >10 cm in 74% of patients and grade was high in 77%. Preoperative IMRT was given to 7 patients (50 Gy) and postoperative IMRT (median dose, 63 Gy) was given to 24 patients. Complete gross resection including periosteal stripping or bone resection was required in 10, and neurolysis or nerve resection in 20. The margins were positive or within 1 mm in 17. Complications from surgery and radiation therapy (RT) were assessed using the Common Terminology Criteria for Adverse Events grading system. RESULTS: Median follow-up time was 23 months. Grade 1 RT dermatitis developed in 71% of patients, Grade 2 in 16%, and Grade 3 in 10%. Infectious wound complications developed in 13% and noninfectious complications in 10%. Two patients (6.4%) developed fractures. Grade 1 neuropathy developed in 28% of patients and Grade 2 in 5%. The rates of Grade 1 and 2 joint stiffness were each 19%. Grade 1 edema was observed in 19% of patients and Grade 2 in 13%. The 2-year local control, distant control, and overall survival were 95%, 65%, and 81%, respectively. CONCLUSION: Intensity modulated RT appears to provide excellent local control in a difficult group of high-risk patients. The morbidity profile is also favorable, but longer follow-up is needed to confirm the results from this study.     

Microvessel density does not predict outcome in high grade soft tissue sarcoma

The induction of new blood vessel growth into tumours from a pre-existing vascular bed (angiogenesis) is a characteristic of virtually all malignant tumours studied. Previous studies have demonstrated a consistent correlation between the extent of angiogenesis and disease prognosis for a wide range of carcinomas, but not for sarcomas. AIMS: To investigate the most appropriate method for assessment of microvessel density (MVD) using a cohort of patients with large (>5 cm), deep (intramuscular), high grade soft tissue sarcoma and investigate any relationship between MVD, vascular endothelial growth factor (VEGF) expression and prognosis. METHODS: Forty-two patients were included in the study. MVD was evaluated in peripheral, central, necrotic and hotspot areas within the tumour by either Chalkley count or total count of immunostained vessels in five high power (x 200) visual fields. RESULTS: Hot spots of angiogenesis were only present in 33% of specimens. There was a strong correlation p<0.001 between the two methods of quantification with Chalkey method being recommended. VEGF expression evaluated by immunohistochemistry was seen in all but one tumour with strong diffuse cytoplasmic staining within tumour cells, which was not correlated with microvessel density, metastasis or survival. There was a positive correlation between MVD and histological subtype (p<0.01), and primary tumour size and the development of metastasis (p=0.049) but MVD was not predictive of metastasis or overall survival. CONCLUSIONS: Unlike the majority of previous studies involving various types of carcinoma, there was no correlation between microvessel density and metastasis or survival in a group of patients with large (>5 cm), deep, high grade soft tissue sarcoma.     

Comparison of conventional radiotherapy and intensity-modulated radiotherapy for post-operative radiotherapy for primary extremity soft tissue sarcoma

Introduction

Doses in conventional radiotherapy for extremity soft tissue sarcoma (STS) potentially exceed normal tissue tolerances. This study compares 3D-conformal radiotherapy (3D-CRT) with intensity-modulated radiotherapy (IMRT) in optimising target volume coverage and minimising integral dose to organs-at-risk (OAR).

Methods and materials

Ten patients undergoing post-operative radiotherapy for extremity STS were assessed. PTV₁ was defined as tumour bed plus 5 cm superiorly/inferiorly and 3 cm circumferentially, PTV₂ was defined as 2 cm isotropically. OAR were defined as whole femur, neurovascular bundle, tissue corridor and normal tissue outside PTV₁. For each patient 2-phase 3D-CRT was compared to 2/3 field (2/3f) and 4/5 field (4/5f) IMRT with simultaneous integrated boost (SIB). The primary planning objective was to minimise femur and skin corridor dose. Volumetric analysis and conformity and heterogeneity indices were used for plan comparison.

Results

A planning protocol containing dose/volume constraints for target and OAR was defined. 4/5f IMRT showed greatest conformity and homogeneity. IMRT resulted in significantly lower femur V45 using 2/3f (p = 0.01) and 4/5f (p = 0.0009) than 3D-CRT. 4/5f IMRT resulted in significantly lower normal tissue V55 (p = 0.004) and maximum dose (p = 0.04) than 3D-CRT.

Conclusions

A reproducible set of planning guidelines and dose-volume constraints for 3D-CRT and IMRT planning for extremity sarcomas was devised. 4/5f IMRT with SIB resulted in better target coverage and significantly decreased OAR dose. Further evaluation of this technique within a clinical trial is recommended to demonstrate that the technical benefit of the more complex technique translates into patient-derived benefit by reducing late toxicity.     

术后放射治疗在原发肢体软组织肉瘤治疗中的作用

分析本院收治的原发于肢体的软组织肉瘤的治疗情况 ,评价术后放射治疗的作用。方法　本院共收治 15 1例 ,可供分析的 139例 ,分析影响生存和局控的因素及术后放射治疗的意义。生存率和局控率用Kaplan Meier方法计算 ,单因素分析用Logrank检验 ,多因素分析用Cox回归方法。结果　全组 5年生存率为 70 .2 % ,10年为 5 0 .4% ;5年无瘤生存率为 5 2 .9% ,10年为41.2 %。单因素分析对全组病例生存率有影响的因素 :肿瘤大小、年龄和治疗方式 (P值分别为0 .0 0 8,0 .0 0 7和 0 .0 40 )。多因素分析只有治疗方式对生存有影响 (P =0 .0 40 )。首次治疗方式对局控影响差异有极显著性 (P <0 .0 1)。手术方式对单纯手术组局控影响差异有极显著性 (P <0 .0 1) ;肿瘤 <5cm时 ,射野大小对术后放射治疗组局控影响差异有极显著性 (P <0 .0 1)。结论　术后放射治疗能提高局部控制率 ,初始射野应相对大 ,并采用缩野技术。对恶性度低、肿瘤 <5cm、手术切缘阴性患者第 1次术后可不做放射治疗。