Long-term outcomes in extremity soft tissue sarcoma after a pathologically negative re-resection and without radiotherapy

BACKGROUND: The purpose was to define the rate of local recurrence (LR) and identify prognostic factors for LR in patients with extremity soft-tissue sarcoma (STS) treated with limb-sparing surgery and a pathologically negative re-resection specimen without radiotherapy (RT). METHODS: A review of the prospective sarcoma database identified 200 patients with primary, nonmetastatic, extremity STS treated with limb-sparing surgery between June 1982 and December 2002 who had a pathologically confirmed negative re-resection. None of the patients had adjuvant RT. Univariate and multivariate analyses were performed to determine clinicopathologic factors associated with LR. RESULTS: With a median follow-up of 82 months the 5-year actuarial LR rate was 9%. Factors associated with higher LR rates on univariate and multivariate analysis were older age, stage III presentation, and histology. The 5-year LR rate was 5% for those<50 compared with 15% for those>or=50 (P=.001). For patients with stage III the LR rate was 26% versus 7% for those with stage I/II (P<.001). On multivariate analysis only age>or=50 (relative risk [RR] 3.3; P=.02) and stage III disease (RR 3.4; P=.01) remained significant predictors for LR. When the cohort of patients was divided into 3 groups based on the number of risk factors present, the 5-year LRs were as follows: no risk factors (stage I/II and<50 years old) 4%, 1 risk factor (stage III or>or=50) 12%, and 2 risk factors (stage III and>or=50) 31% (P<.01). CONCLUSIONS: Patients with a pathologically negative re-excision represent a heterogeneous group. Whereas the overall rate of local recurrence at 5 years was 9% for the entire cohort, patients with older age and/or stage III disease had a higher rate of LR. Therefore, treatment decisions especially with regard to adjuvant RT should be individualized and not be based solely on the finding of a negative re-resection.     

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。      

Clinical outcomes for patients with soft tissue sarcoma of the hand

BACKGROUND:

In an earlier report from the current study center regarding surgical treatment for patients with soft tissue sarcoma (STS) of the hand, it was concluded that repeat resection or amputation improves outcomes. Since then, the authors have aggressively sought to achieve negative resection margins, using standard or modified amputations when needed, and performing repeat resections to negative surgical margins when they were not achieved at the time of initial surgery. The current review was conducted to determine whether this approach resulted in better outcomes.

METHODS:

A retrospective review of 53 patients with STS of the hand who were treated between 1996 and 2005 was performed. Recurrence‐free survival (RFS) and functional outcome of hand‐preserving procedures were assessed according to the Musculoskeletal Tumor Society (MSTS) system.

RESULTS:

The median RFS was not reached at the time of last follow‐up. Of 53 patients, 6 (11%) had positive microscopic resection margins. Three patients underwent repeat resection to negative surgical margins, whereas another 3 patients did not. All 3 patients with positive microscopic surgical margins that were not re‐excised developed local disease recurrence; 2 patients also developed distant metastases. Two of the 50 patients with negative resection margins developed distant metastases. All 5 patients who developed local and/or distant disease recurrence had deep tumors. The median MSTS score was 29 (interquartile range, 27‐30). Patients who underwent more extensive resections, such as double ray amputations, had lower MSTS scores.

CONCLUSIONS:

Suboptimal biopsies and positive resection margins are associated with local and distant disease recurrence in patients with STS. The results of the current study suggest that aggressive surgical treatment can result in better clinical outcomes, and underscore that care must be taken when planning biopsies of hand tumors. Cancer 2011. © 2010 American Cancer Society.     

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。     

血管重建在软组织肉瘤累及肢体主要血管时的应用

目的:探讨人工血管重建对肢体软组织肉瘤累及大血管的保肢手术的临床意义。方法:收集2012年至2022年间我院所做的5例人工血管重建保肢手术案例资料,并结合文献进行分析。结果:所纳入5例患者均行肉瘤整体切除联合人工血管重建。其中平滑肌肉瘤2例,未分化多形性肉瘤1例,去分化脂肪肉瘤1例,侵袭性纤维瘤病1例;累及股动脉3例,股静脉3例,锁骨下动脉1例;累及臂丛神经1例,股神经1例。随访期间出现局部复发2例,远处转移2例,其中1例因多次复发转移行3次手术治疗;出现血管闭塞1例,行血管内介入手术后开通,余4例通畅;1例患者随访4月后死亡,最长随访时间10年。结论:肉瘤的生物学行为特征是影响血管重建的关键因素,同时对周围神经的保护也需要重视。     

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.     

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。     

Radiation planning comparison for superficial tissue avoidance in radiotherapy for soft tissue sarcoma of the lower extremity

PURPOSE: Three types of preoperative radiotherapy (RT) plans for extremity soft tissue sarcoma were compared to determine the amount of dose reduction possible to the planned surgical skin flaps required for tumor resection and wound closure, without compromising target coverage. METHODS AND MATERIALS: Twenty-four untreated patients with large, deep, lower extremity STS treated with preoperative RT and limb salvage surgery had their original conventional treatment plans re-created. The same clinical target volume was used for all three plans. The future surgical skin flaps were created virtually through contouring by the treating surgeon and regarded as an organ at risk. The original, conformal, and intensity-modulated RT (IMRT) plans were created to deliver 50 Gy in 25 fractions to the clinical target volume. Clinical target volume and organ-at-risk dose-volume histograms were calculated and the plans compared for conformality, target coverage, and dose sparing. RESULTS: The mean dose to the planned skin flaps was 42.62 Gy (range, 30.24-48.65 Gy) for the original plans compared with 40.12 Gy (range, 24.24-47.26 Gy) for the conformal plans and 26.71 Gy (range, 22.31-31.91 Gy) for the IMRT plans (p = 0.0008). An average of 86.4% (range, 53.2-97.4%) of the planned skin flaps received >or=30 Gy in the original plans compared with 83.4% (range, 36.2-96.2%) in the conformal plans and only 34.0% (range, 22.5-53.3%) in the IMRT plans (p = 0.0001). IMRT improved target conformality compared with the original and conformal plans (1.27, 2.34, and 1.76, respectively, p = 0.0001). CONCLUSION: In a retrospective review, preoperative IMRT substantially lowered the dose to the future surgical skin flaps, sparing a greater percentage of this structure's volume without compromising target (tumor) coverage.     

Phase 2 study of preoperative image‐guided intensity‐modulated radiation therapy to reduce wound and combined modality morbidities in lower extremity soft tissue sarcoma

BACKGROUND:

This study sought to determine if preoperative image‐guided intensity‐modulated radiotherapy (IG‐IMRT) can reduce morbidity, including wound complications, by minimizing dose to uninvolved tissues in adults with lower extremity soft tissue sarcoma.

METHODS:

The primary endpoint was the development of an acute wound complication (WC). IG‐IMRT was used to conform volumes to avoid normal tissues (skin flaps for wound closure, bone, or other uninvolved soft tissues). From July 2005 to June 2009, 70 adults were enrolled; 59 were evaluable for the primary endpoint. Median tumor size was 9.5 cm; 55 tumors (93%) were high‐grade and 58 (98%) were deep to fascia.

RESULTS:

Eighteen (30.5%) patients developed WCs. This was not statistically significantly different from the result of the National Cancer Institute of Canada SR2 trial (P = .2); however, primary closure technique was possible more often (55 of 59 patients [93.2%] versus 50 of 70 patients [71.4%]; P = .002), and secondary operations for WCs were somewhat reduced (6 of 18 patients [33%] versus 13 of 30 patients [43%]; P = .55). Moderate edema, skin, subcutaneous, and joint toxicity was present in 6 (11.1%), 1 (1.9%), 5 (9.3%), and 3 (5.6%) patients, respectively, but there were no bone fractures. Four local recurrences (6.8%, none near the flaps) occurred with median follow‐up of 49 months.

CONCLUSIONS:

The 30.5% incidence of WCs was numerically lower than the 43% risk derived from the National Cancer Institute of Canada SR2 trial, but did not reach statistical significance. Preoperative IG‐IMRT significantly diminished the need for tissue transfer. RT chronic morbidities and the need for subsequent secondary operations for WCs were lowered, although not significantly, whereas good limb function was maintained. Cancer 2013. © 2013 American Cancer Society.     

The clinical and functional outcome for patients with radiation-induced soft tissue sarcoma

BACKGROUND:

Radiation‐induced soft tissue sarcomas (RI‐STS) are rare, and it is believed that they are associated with a poor prognosis.The authors of this report compared the clinical and functional outcomes of adults who had extremity RI‐STS with the outcomes of adults with sporadic STS.

METHODS:

Forty‐four patients who were diagnosed with RI‐STS from 1989 to 2009 were identified from 4 prospectively collected databases. Patient demographics, surgical and adjuvant treatment parameters, and oncologic and functional outcomes were evaluated.

RESULTS:

The median latent period from irradiation of the primary condition to RI‐STS diagnosis was 16 years. The median radiotherapy dose used for the index condition was 45 gray. The median age at RI‐STS diagnosis was 56 years. The most common primary diagnoses were breast cancer (36.4%) and lymphoma (34.1%). The most common RI‐STS histologies were malignant fibrous histiocytoma (36.4%) and angiosarcoma (18.2%). Forty‐two patients underwent surgery, 13 patients received adjuvant radiotherapy, and 8 patients received adjuvant chemotherapy. Systemic metastases occurred in 50% of treated patients (n = 21), and 26% (n = 11) developed local recurrence, the risk of which was lower among patients who received reirradiation (P = .043). The 5‐year disease‐free interval (DFI) and overall survival (OS) rates for patients with RI‐STS who presented without metastasis were 36% and 44%, respectively. Patients who had International Union Against Cancer TNM stage III RI‐STS had a significantly worse DFI compared with patients who had stage III sporadic STS (multivariate analysis, P = .051). Eighteen patients with RI‐STS underwent functional assessment after surgery, and their results were comparable to those of patients with sporadic STS.

CONCLUSIONS:

Despite aggressive surgical treatment, patients who have RI‐STS remain at greater risk of both local and systemic recurrence compared with patients who have sporadic STS, but they can anticipate similar functional outcomes. Reirradiation can be relatively safe and effective if used properly. Cancer 2011. © 2011 American Cancer Society.     

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.     

Results of limb-salvage surgery with vascular reconstruction for soft tissue sarcoma in the lower extremity: comparison between only arterial and arterovenous reconstruction

BACKGROUND: Reports on vascular reconstruction in conjunction with limb salvage techniques for soft tissue sarcomas in the lower extremity have been published. The aim of this study was to investigate the necessity for venous reconstruction by comparing the results of arterial reconstruction alone and those of arteriovenous reconstruction. METHODS: Twenty-five (6.7%) of 373 patients underwent vascular resections for lower limb soft tissue sarcomas. Only arterial reconstruction was performed for 12 patients. Arteriovenous reconstruction was performed for 13 patients. The clinical results, complications, and postoperative function were compared between only arterial reconstruction group and arteriovenous reconstruction group. RESULTS: Limb salvage was achieved in 92% of all cases. No local recurrence has been observed. Nineteen patients (76%) are continuously free of disease. Histopathologic examination of the specimens showed that blood vessels had been infiltrated in 24%. The mean Musculoskeletal Tumor Society score was 70%. There were no significant differences in complication rate and postoperative function between two groups. CONCLUSIONS: Wide resection with vascular reconstruction for patients of soft tissue sarcomas involving major vessels in the lower limb provide long term local control and limb salvage. This study could not indicate the usefulness of additional venous reconstruction after vascular resection in the lower extremity.     

184例软组织肉瘤患者不同治疗方法分析

目的 探讨软组织肉瘤适当的治疗方法。方法 总结184例软组织肉瘤患者的临床资料,分析单纯手术(94例)、手术后加辅助放疗(62例)、手术后加辅助化疗(28例)的长期生存率和影响预后的因素。结果 单纯手术、手术后加辅助放疗和手术后加辅助化疗患者的5年生存率分别为39.4％、48.4％和28.6％。综合治疗是提高患者牛仔率与改善乍活质量的关键。临床分期、病理类型及治疗方法足影响长期生存的重要因素。结论 软组织肉瘤术后辅助放疗可以提高患者5年生存率。     

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。     

Preoperative radiation,surgical margins,and local control of extremity sarcomas of soft tissues

The relationship between status of the surgical margin and local control of soft tissue sarcoma of the extremities by preoperative radiation therapy has been assessed in 132 consecutive patients from 1974 to 1988. The 5-year actuarial local control rate was 94% for all patients; the rates were 97% and 82% for the 104 tumors with negative marigins and the 28 tumors with positive margins, respectively. The local control rate was independent of the extent of the negative margin. For primary sarcomas, the local control rates were 96%, 97%, and 100%, respectively, for margins that were negative at ≤1 mm or > 1 mm, or the specimens were negative for tumor; for positive margins the results was 83%. The overall local control rate was lower (not significant) for recurrent than for primary sarcomas: 88% vs. 94%. On the other hand, when stratifying by margin status, no difference was observed in local control results, i.e.: (1) 97% and 91% for primary and recurrent tumors with negative margins, respectively, and (2) 83% and 80% for primary and recurrent tumors with positive margins, respectively. Local control was not significantly higher in those patients who were treated by surgical resection (S), radiation (RT), and re-excision of the previous tumor bed than in those whose radiation therapy was started after the biopsy and followed by one surgical resection. For primary sarcomas that were resected with negative margins the results were: 100% of 15 patients treated by S-RT-S and 96% of 75 patients treated by RT-S. © 1993 Wiley-Liss, Inc.     

Adjuvant role of radiation in soft tissue sarcoma in adults.

Forty-seven patients with soft tissue sarcomas were analyzed retrospectively. Treatment was non-randomized between surgery alone, preoperative radiation of 5,000 rads/5 weeks, postoperative radiation of 6,000 rads/6 weeks following total gross tumor removal, and postoperative radiation (variable dosees) for residual gross or unresectable tumor. Preoperative radiation was not statistically better for local control or survival compared to postoperative radiation after local excision of gross tumor. Wide excision, higher postoperative radiation dosage, and/or enlarged radiation portals perhaps would improve results. Additional adjuvant therapies, such as chemotherapy or immunotherapy, needs to be investigated.