Limb sparing approach: adjuvant radiation therapy in adults with intermediate or high-grade limb soft tissue sarcoma.

BACKGROUND: Limb soft tissue sarcomas (STS) are currently treated with limb sparing surgery (LSS) followed by radiation therapy (RT). PATIENTS AND METHODS: Between October 1994 and October 2002, 133 adult patients with intermediate or high-grade limb STS were approached by LSS+RT. RESULTS: RT related toxicity was manageable, with a low rate of severe effects. At 4-year median follow-up, there were 48 recurrences of any type, 23 of isolated local failure, and 35 of systemic spread w/o local failure. DFS and OS were influenced by disease stage II vs I, primary site in the upper limb vs lower limb, MPNST vs other types, induction therapy vs no induction, adequate resection vs marginal resection or involved margins, and good response to induction therapy vs bad response. DFS and OS were Patient's age and sex, tumor depth, acute or late toxicity of RT, or the interval of time between the date of definitive surgery and the start of RT did not affect DFS and or OS. CONCLUSIONS: The RT protocol is applicable in the era of complicated, expensive and time-consuming 3D therapy. Our results of LSS+RT in adults with limb HG STS are satisfactory.     

Palliative surgery of soft tissue sarcoma

Despite an increasing trend towards early diagnosis of breast cancer,patients still present with locally advanced disease. Also, in some patients chemotherapy will fail, and local and regional recurrence will occur. This article outlines options for palliative care for such patients.     

Limb function following conservation treatment of adult soft tissue sarcoma

Quality of life and limb function were studied in 54 patients who were disease-free 2 or more years after limb-conserving treatment for soft tissue sarcoma of the leg or pelvic girdle. Tumours of the thigh predominated (25 patients) and the mean tumour size was 9.9 cm. 41 patients had been treated with a combination of surgery and radiotherapy (29 with conventional and 12 with high dose), 12 with surgery alone and one with irradiation and intra-arterial doxorubicin. Only 15 patients had a normal range of movement in all lower limb joints and only 12 had normal power in all muscle groups; tumours of the lower leg were particularly unfavourable in this respect. Gait was normal in 42 patients but 8 required a walking aid and 4 a joint support. 16 had detectable lymphoedema but only 2 needed to wear compression hosiery. 35 patients still experienced pain at some time but only 6 required analgesia. However, when assessed by questionnaire for locomotion, grooming and home/leisure/vocational activities, 37 patients (68%) reported excellent function, and only 2 had moderate impairment. Function loss was most marked in leisure (25 patients) and vocational (8) activities, but was mild in 66% of cases. Multivariate analysis was carried out to determine the prognostic factors for poor limb function. The results suggested that overall functional score was predominantly determined by gait (P < 0.001), muscle power or range of movement (P < 0.001), with increasing age, female sex and the use of radiotherapy poor prognostic factors. Reduced muscle power or range of movement were the major factors determining gait (P < 0.02) with the use of radiotherapy the significant prognostic factor for both in the conventionally treated group. Doses in excess of 60 Gy resulted in increased fibrosis and a worse functional outcome. Extent of surgery was not an independent prognostic factor for limb function, although univariate analysis suggested an association with range of movement in the conventionally treated group (P < 0.025). Despite significant objective loss of range of movement and muscle power patients retain excellent limb function and quality of life following limb conserving treatment. For optimal function, radiotherapy should be given with small fractions to a dose not exceeding 60 Gy.     

同期小野补量放疗肢体软组织肉瘤的临床研究

目的　探讨同期小野补量放疗技术在肢体软组织肉瘤治疗中的作用及疗效。方法　86例肢体软组织肉瘤术后患者随机分为研究组4 5例和对照组4 1例。研究组大野4 5～5 0Gy/4.5～5 .0周,小野2 0～30Gy/3～4周,每天2个野轮照,间隔6h以上;对照组大野4 5～5 0Gy/4.5～5 .0周后缩野加量2 0～30Gy/2～3周。结果　研究组和对照组1、3、5年生存率分别为90 .6 %和85 .4 %、86 .7%和72 .9%、73.3%和6 5 .0 % (P >0 .0 5 ) ;1、3、5年局部复发率分别为4 .4 %和9.8%、8.9%和2 6 .8%、13.3%和32 .6 % (P <0 .0 5 )。研究组和对照组急、慢性放射性皮肤损伤、慢性放射性皮下组织损伤发生率分别为6 0 .0 %和4 1.5 %、80 .0 %和6 3.4 %、77.8%和6 5 .9% (P >0 .0 5 )。结论　同期小野补量照射技术不增加放射性损伤,但能明显降低局部复发率、提高生存率。     

Limb salvage by neoadjuvant isolated perfusion with TNFalpha and melphalan for non-resectable soft tissue sarcoma of the extremities.

AIMS: Patients with non-resectable soft tissue sarcomas of the extremities do not live longer if they are treated by amputation or disarticulation. In order to avoid major amputations, we tested isolated limb perfusion (ILP) with tumour necrosis factor alpha (TNF)+melphalan+/-interferon-gamma (IFN) as a pre-operative, neoadjuvant limb salvage treatment. METHODS: Twenty-two patients were included (six men and 16 women; three upper limb and 19 lower limb tumours). The AJCC stage was IIA in four patients, III in seven and IV in 11. Thirteen cases were recurrent or progressive after previous therapy; five tumours had a diameter >/=20 cm, and four were multiple or regionally metastatic. There were six malignant fibrous histiocytomas, five liposarcomas, four malignant peripheral nerve sheath tumours, three rhabdomyosarcomas, two leiomyosarcomas, one recurrent extraskeletal osteosarcoma and one angiosarcoma. RESULTS: Twenty-four ILPs were performed in the 22 patients, and 18 (82%) experienced an objective response: this was complete in four (18%) and partial in 14 (64%). Three patients had a minimal or no response and the tumour progressed in one case. All patients had fever for 24 hours but only one developed a reversible grade 3 distributive shock syndrome with no sequelae. There was no grade 4 toxicity. Seventeen patients (77%) underwent limb-sparing resection of the tumour remnants after a median time of 3.4 months: 10 resections were intracompartmental and seven extracompartmental. Surgery included flaps or skin grafts in five patients, arterial replacement in two and knee arthrodesis in one. Adjuvant chemotherapy was given to eight patients and radiotherapy to six. In one patient amputation was necessary after a second ILP. Secondary amputations were performed for recurrence in two patients, resulting in an overall limb salvage rate of 19/22 (86%). After a median follow-up of 18.7 months, 10 recurrences were recorded: seven were both local and systemic and three were only local. The median disease free and overall survival times have been >12.5 and 18.7 months respectively: this is similar to the outcome after primary amputations for similar cases. CONCLUSION: ILP with TNF and chemotherapy is an efficient limb sparing neoadjuvant therapy for a priori non-resectable limb soft tissue sarcomas.     

肢体恶性软组织肿瘤的保肢治疗

目的 探讨四肢恶性软组织肿瘤保肢治疗的可行性。方法 22例肢体恶性软组织肿瘤患者中,滑膜肉瘤9例,横纹肌肉瘤及恶性纤维组织细胞瘤各5例。透明细胞肉瘤2例,恶性黄色肉芽肿1例。其中股部9例,臀部4例,膝部、足跟部各3例,小腿外侧、腕部、足背部各1例。16例行肿瘤扩大切除术,6例行肿瘤扩大切除皮瓣修复术。术后采用CVADIC方案行化疗,16例行放疗。结果 19例获得平均4年2个月的随访,2例复发,2例死亡(1例为复发后再次手术患者)。结论 肿瘤切除彻底是四肢恶性软组织肿瘤保肢治疗的前提;放疗可以改善局部控制率;CVADIC方案是治疗恶性软组织肿瘤的可行方案;肿瘤切除后软组织缺损修复,应选择操作简单、就近取材、效果良好的方法。     

Safe-margin surgery by plastic reconstruction in extremities or parietal trunk soft tissue sarcoma: A tertiary single centre experience

IntroductionTertiary centers recruit a large proportion of locally advanced or recurrent soft tissue sarcomas (STSs) that may have been preoperatively irradiated. The objective of this study was to evaluate the results of oncoplastic surgery (OPS) for patients affected by extremities or parietal trunk STS.Materials and methodsThis retrospective study includes patients who underwent a flap reconstruction after sarcoma resection between January 2018 and December 2020 at Institut Curie. The primary endpoint was the evaluation of the impact of OPS on the quality of surgical margins. The secondary endpoint was to quantify the morbidity of OPS and identify predictive factors for wound complications.ResultsOf 211 patients, 89 (42.2%) had a flap reconstruction. Surgery was realized on an irradiated field in 56 (62.9%) patients. Without OPS, all patients were candidates either for amputation (n = 9,10.1%) due to vessels/nerve infiltration, or R1/R2 resection (n = 80,89.9%). Seventy-two (80.0%) pedicle flaps and 18 (20.0%) free flaps were used. No R2 resections were performed. R0 and R1 margins were achieved in 82 (92.1%) and 7 (7.9%), respectively. The median closest margin was 3 mm (IQR 1–6 mm). Among R1 patients, 5 had positive margins along a preserved critical structure, 2 patients had well-differentiated liposarcomas. The surgical morbidity rate was 33.3% (30/90 flaps). The reoperation rate was 15.7% (14/89 patients).ConclusionsIn a referral sarcoma center, the collaboration between the surgical oncologist and the plastic surgery team should be considered upfront in the surgical plan, allowing the most adequate wide oncological resection with acceptable postoperative morbidity.     

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。     

Long-term outcomes after function-sparing surgery without radiotherapy for soft tissue sarcoma of the extremities and trunk.

PURPOSE: To define the rate of local recurrence (LR) and identify prognostic factors for LR for patients with soft tissue sarcoma (STS) treated with function-sparing surgery (FSS) without radiotherapy (RT). PATIENTS AND METHODS: Between 1970 and 1994, 242 patients with STS of the trunk and extremity presented with primary localized disease, 74 of whom were treated with FSS without RT (31%). The median tumor size was 4 cm (range, 0.5 to 31 cm). There were 40 patients with grade 1 tumors and 34 with grade 2 and 3 tumors. Median follow-up was 126 months. RESULTS: The 10-year actuarial local control rate was 93% +/- 4%. Resection margin status was a significant predictor for LR. Patients with closest histologic resection margins of less than 1 cm had a 10-year local control rate of 87% +/- 6% compared with 100% for patients with closest histologic resection margins of >/= 1 cm (P =.04). There was no significant association between LR and tumor grade, size, site (truncal v extremity), or depth (superficial v deep). For all patients, the 10-year actuarial survival rate was 73% +/- 6%. CONCLUSION: The 7% LR rate after treatment of STS with FSS without RT reported herein is comparable to published rates following treatment where adjuvant RT is used. These results suggest there may be a select subset of patients with STS in whom carefully performed FSS may serve as definitive therapy and in whom adjuvant RT may not be necessary. However, further study is needed to carefully define this subset of patients and to identify the optimal surgical approach and technique for patients treated without RT.     

Processes and outcomes of care for soft tissue sarcoma of the extremities

Purpose: A population-based cohort study of soft tissue sarcoma of the extremities (STSE) in Ontario, Canada was conducted using linked administrative databases.Methods and materials: Electronic administrative databases were linked from the Ontario Cancer Registry, the Canadian Institute for Health Information, and Radiation Oncology Research Unit database of radiation therapy (RT) records.Results: The definitive surgery was amputation for 6.0%, resection for 60.9%, biopsy for 7.5%; the remainder had no surgical record. Adjuvant RT was administered to 40.2% of cases. Among cases initially treated by surgical resection, 2.0% later underwent amputation and 9.5% underwent further resection during follow-up. The adjusted odds ratio (OR) for amputation as definitive surgery was 2.3 (1.19, 4.45) in eastern Ontario relative to Toronto. The likelihood of adjuvant RT among those not registered at a cancer centre within 3 months of diagnosis was decreased (OR = 0.20 (95% CI (0.13, 0.30)) relative to those registered. The adjusted relative risk of amputation at any time following diagnosis was 3.48 (95% CI (1.63, 7.46)) among cases not attending a cancer centre. The adjusted relative risk of death was 1.4; 95% CI (1.1, 1.7) among those not attending a cancer centre.Conclusions: Cases not seen at a multidisciplinary cancer centre within 3 months following diagnosis of STSE have an increased relative risk for amputation at any time, and for death due to any cause. Many hypotheses for further study are suggested by the results of this analysis.     

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.     

肢体骨和软组织肉瘤的化疗进展(二)

成骨肉瘤 成骨肉瘤是一种罕见的肿瘤,好发年龄在10-30岁间,男性多于女性。好发部位是股骨下段、胫骨上段和肚骨上段。在初诊时,发现约有20%的病例肿瘤已发生全身转移     

Surgery in soft tissue sarcoma: more conservative in extremities,more extended in the retroperitoneum

Extremity soft-tissue sarcomas (ESTS) account for approximately 50% and retroperitoneal soft-tissue sarcomas (RSTS) for approximately15% of all soft-tissue sarcomas. Surgery remains the main treatment modality for all soft-tissue sarcomas. Neoadjuvant and/or adjuvant chemo-and radiation-therapy are also often used to improve the treatment outcomes. In ESTS, surgery had originally been mutilating. The introduction of principles of surgical adequacy and of complementary treatments, especially radiotherapy, led to a reduction in the amputation rate in favor of conservative treatments. The implementation of plastic, vascular and nerve reconstructions allowed for further increase in conservative procedures, with better functional and cosmetic results. Moreover, recent reports have demonstrated how preoperative treatments can offset the negative prognostic impact of marginal resection on local outcome and survival, extending the limit of limb and function preservation. In RSTS, surgery had consisted of simple excision, while the resection of surrounding organs/viscera had been considered only in cases of direct involvement/infiltration. This strategy was associated with a high rate of local recurrence, which in many cases it was the driving cause of death. In order to improve local control and subsequent overall survival, some authors have recently advocated a policy of extended surgery including surrounding organs/viscera en bloc with the tumor. In this review, the authors discuss the standard world wide accepted surgical treatment for ESTS and the new surgical approach for RSTS.     

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.     

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.     

Limb salvage surgery for bone and soft tissue sarcoma. A phase II pathologic study of preoperative intraarterial cisplatin.

Preoperative therapy has been tested as part of limb salvage therapy for localized bone and soft tissue sarcoma of the extremities. The activity of cisplatin (CDDP) by intraarterial (IA) infusion was evaluated in 40 cases of which 36 were evaluable for response. All patients had high-grade sarcomas. All but 3 patients received 3 or 4 courses (24 patients received 4 courses) of CDDP at a dosage of 120 to 150 mg/m2 given over 6 hours every 2 weeks by IA infusion. Patients younger than 18 years of age received the higher dose of CDDP. Treatment was well tolerated with combination antiemetics. One patient experienced severe hearing loss with the first cycle of the higher CDDP dose. Pathologic evaluation of resected osteosarcoma showed a favorable response (90% or greater necrosis) in 8 of 20 evaluable cases and in 3 of 4 patients with malignant fibrous histiocytoma (MFH) of bone (without osteoid). In soft tissue sarcomas, minimal (50% to 89%) necrosis was seen in two of nine cases and none had 90% or greater necrosis. Patients received postoperative chemotherapy based on pathologic response, but the value of this postoperative adjuvant therapy requires further follow-up and is uncertain in this small study. IA CDDP can often cause significant tumor necrosis in patients with bone sarcomas, whereas soft tissue sarcomas are less sensitive to this therapy.