Complete pathological response to neoadjuvant treatment is associated with better survival outcomes in patients with soft tissue sarcoma: Results of a retrospective multicenter study

BackgroundLocally advanced soft tissue sarcoma (STS) management may include neoadjuvant or adjuvant treatment by radiotherapy (RT), chemotherapy (CT) or chemoradiotherapy (CRT) followed by wide surgical excision. While pathological complete response (pCR) to preoperative treatment is prognostic for survival in osteosarcomas, its significance for STS is unclear. We aimed to evaluate the prognostic significance of pCR to pre-operative treatment on 3-year disease-free survival (3y-DFS) in STS patients.MethodsThis is an observational, retrospective, international, study of adult patients with primary non-metastatic STS of the extremities and trunk wall, any grade, diagnosed between 2008 and 2012, treated with at least neoadjuvant treatment and surgical resection and observed for a minimum of 3 years after diagnosis. The primary objective was to evaluate the effect of pCR. (≤5% viable tumor cells or ≥95% necrosis/fibrosis) on 3y-DFS. Effect on local recurrence-free survival (LRFS), distant recurrence-free survival (MFS) overall survival (OS) at 3 years was also analyzed. Statistical univariate analysis utilized chi-square independence test and odds ratio confidence interval (CI) estimate, multivariate analysis was performed using LASSO.ResultsA total of 330 patients (median age 56 years old, range:19–95) treated by preoperative RT (67%), CT (15%) or CRT (18%) followed by surgery were included. pCR was achieved in 74/330 (22%) of patients, of which 56/74 (76%) had received RT. 3-yr DFS was observed in 76% of patients with pCR vs 61% without pCR (p < 0.001). Multivariate analysis showed that pCR is statistically associated with better MFS (95% CI, 1.054–3.417; p = 0.033), LRFS (95% CI, 1.226–5.916; p = 0.014), DFS (95% CI, 1.165–4.040; p = 0.015) and OS at 3 years (95% CI, 1.072–5.210; p = 0.033).ConclusionsIn a wide, heterogeneous STS population we showed that pCR to preoperative treatment is prognostic for survival.     

术中置管近距离放疗在骨与软组织肉瘤治疗中的应用

目的分析术中置管近距离放疗在骨与软组织肉瘤综合治疗中应用的疗效和毒性。方法163例骨与软组织肉瘤的病例，其中59例采用手术＋化疗＋外照射，另外104例采用手术＋化疗＋近距离放疗＋夕h照射的综合治疗方法。结果采用近距离放疗的一组患者有较好的疗效和较低的毒性。结论术中置管近距离放疗在骨与软组织肉瘤的综合治疗中有较好临床应用价值．．     

Multidisciplinary treatment of soft tissue sarcomas: An update

Standard treatment for soft tissue sarcoma, based on complete surgical resection with or without adjuvant radiotherapy and chemotherapy, has not substantially changed during the last several decades. Nevertheless, recent advances have contributed to considerable improvement in the management of these patients; for example, new magnetic resonance imaging sequences such as diffusion-weighted imaging and magnetic resonance imaging radiomics can better assess tumor extension and even estimate its grade. Detection of circulating genetic material (liquid biopsy) and next-generation sequencing are powerful techniques for genetic analysis, which will increase our understanding of the underlying molecular mechanisms and may reveal potential therapeutic targets. The role of chemotherapy in non-metastatic disease is still controversial, and there is a need to identify patients who really benefit from this treatment. Novel chemotherapeutic regimens have entered clinical praxis and can change the outcome of patients with metastatic disease. Advances in radiotherapy have helped decrease local adverse effects and sustain good local control of the disease. The following report provides an updated view of the diagnosis, treatment, and future perspectives on the management of patients with soft tissue sarcomas.     

Trabectedin in patients with advanced soft tissue sarcoma: A retrospective national analysis of the French Sarcoma Group

AimThe French Sarcoma Group performed this retrospective analysis of the ‘RetrospectYon’ database with data of patients with recurrent advanced soft tissue sarcoma (STS) treated with trabectedin 1.5 mg/m² as a 24-h infusion every three weeks.MethodsPatients who achieved non-progressive disease after six initial cycles could receive long-term trabectedin treatment until disease progression.ResultsOverall, 885 patients from 25 French centres were included. Patients received a median of four trabectedin cycles (range: 1–28). The objective response rate was 17% (six complete/127 partial responses) and 50% (n = 403) of patients had stable disease for a disease control rate of 67%. After a median follow-up of 22.0 months, median progression-free survival (PFS) and overall survival (OS) were 4.4 and 12.2 months, respectively. After six cycles, 227/304 patients with non-progressive disease received trabectedin until disease progression and obtained a significantly superior median PFS (11.7 versus 7.6 months, P < 0.003) and OS (24.9 versus 16.9 months, P < 0.001) compared with those who stopped trabectedin treatment. Deaths and unscheduled hospitalisation attributed to drug-related events occurred in 0.5% and 9.4% of patients, respectively.ConclusionThe results of this real-life study demonstrate that treatment with trabectedin of patients with STS yielded comparable or improved efficacy outcomes versus those observed in clinical trials. A long-term treatment with trabectedin given until disease progression is associated with significantly improved PFS and OS.     

软组织肉瘤的诊断与综合治疗

软组织肉瘤(STS)是一种来源广泛、组织学各异、罕见的恶性肿瘤.其诊断的基础依赖于光镜下的形态表现,特殊染色、免疫组化及电镜观察是其病理诊断的有益补充,结合临床如年龄、肿瘤大小、部位、生长方式等,以综合判断从而能做出正确的诊断.外科手术是治疗软组织肉瘤的主要方式,辅助放疗能控制肿瘤的局部复发,现代治疗软组织肉瘤,尤其病灶位于四肢者,崇尚综合治疗.辅助化疗的作用仍有争议,但有Meta分析证实辅助化疗能提高无病生存和总生存率,特别是位于四肢者.化疗对晚期STS有一定作用,以ADM、IFO为主的强化治疗能产生较好的疗效,但选择标准更为严格.开发新的靶向治疗药物是改善STS预后的关键.     

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.     

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.     

浅谈软组织肉瘤的误诊和误治

软组织肉瘤(soft tissue sarcoma,STS)是来源于间叶组织可发生于全身各部位的恶性肿瘤,发病率较低,约占全部恶性肿瘤的0.8%~1.0%[1]。近年来,随着STS诊断技术的提高、手术方法的改进、新的抗肿瘤药物的问世和新的联合化疗方案的应用,STS的诊治不断规范,其预后已经有了明显的改善。目前,国内STS患者一般是在肿瘤医院专科接受诊治,但仍有部分患者是在综合医院的骨科或普通外科接受诊治。由于     

Adherence to consensus-based diagnosis and treatment guidelines in adult soft-tissue sarcoma patients: a French prospective population-based study

BackgroundSoft-tissue sarcomas (STSs) are rare tumors with varied histological presentations. Management and treatment are thus complex, but crucial for patient outcomes. We assess adherence to adult STS management guidelines across two French regions (10% of the French population). We also report standardized incidence.Patients and methodsSTS patients diagnosed from 1 November 2006 to 31 December 2007 were identified from pathology reports, medical hospital records, and cancer registries. Guideline adherence was assessed by 23 criteria (validated by Delphi consensus method), and age and sex-standardized incidence rates estimated. Associations between patient, treatment, and institutional factors and adherence with three major composite criteria relating to diagnostic imaging and biopsy as well as multidisciplinary team (MDT) case-review are reported.ResultsTwo hundred and seventy-four patients were included (57.7% male, mean age 60.8 years). Practices were relatively compliant overall, with over 70% adherence for 10 criteria. Three criteria with perfect Delphi consensus had low adherence: receiving histological diagnosis before surgery, adequacy of histological diagnosis (adherence around 50% for both), and MDT discussion before surgery (adherence <30%). Treatment outside of specialized centers was associated with lower adherence for all three composite criteria, and specific tumor sites and/or features were associated with lower adherence for diagnostic imaging, methods, and MDT meetings. STS standardized incidence rates were 4.09 (European population) and 3.33 (World) /100 000 inhabitants.ConclusionsInitial STS diagnosis and treatment across all stages (imaging, biopsy, and MDT meetings) need improving, particularly outside specialized centers. Educational interventions to increase surgeon's sarcoma awareness and knowledge and to raise patients' awareness of the importance of seeking expert care are necessary.     

Outcomes of isolated limb perfusion in the treatment of extremity soft tissue sarcoma: A systematic review

Background

Isolated limb perfusion (ILP) may provide a limb salvage option for locally advanced soft tissue sarcoma (STS) not amenable to local resection.

Methods

A systematic review was performed for studies reporting outcome of ILP for locally advanced STS performed after 1980 in patients aged ≥12 years old. The main endpoints were tumour response and limb salvage rates. Complication and recurrence rates were secondary endpoints.

Results

Eighteen studies were included, providing outcomes for 1030 patients. Tumour necrosis factor-alpha with melphalan was the commonest chemotherapy regime. When reported, 22% of cases achieved a complete tumour response (216/964, 15 studies) with an overall response rate of 72% (660/911, 15 studies). At median follow-up times ranging between 11 and 125 months, the limb salvage rate was 81% in patients who otherwise would have been subjected to amputation. However, 27% of patients suffered local recurrence and 40% suffered distant failure. ILP was associated with severe locoregional reactions in 4% (22/603) of patients. Amputation due to complications within 30 days was necessary in 1.2% of cases (7/586, nine studies). There was insufficient evidence to determine the effect of ILP on survival.

Conclusion

ILP induces a high tumour response rate, leads to a high limb salvage rate but is associated with a high recurrence rate. It provides a limb salvage alternative to amputation when local control is necessary.     

Significance of local treatment in patients with metastatic soft tissue sarcoma

Metastatic soft tissue sarcomas (STS) represent enormous challenges to improve the low survival rate, which is almost the same as past 2 decades ago, although surgery, radiotherapy and radiofrequency ablation has been accepted in the treatment of metastatic STS. Moreover, STS varies between elderly and younger victims in the aspect of diagnoses, prognosis, and treatment strategies. In order to evaluate the role of local treatment in improving prognosis for patients with metastatic STS and select the proper candidates who will benefit from local therapy, a single-institution nearly 50-year experience were collected and reviewed. Finally, we found that local treatments could improve treatment response and survival, but overall survival advantage could not be seen in elderly patients. This conclusion from a single institution could serve as a basis for future prospective multi-institutional large-scale studies.     

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.     

Histopathological outcome of 597 isolated soft tissue tumors suspected of soft tissue sarcoma: a single-center 12-year experience.

BACKGROUND: The aim of this present report was to analyze the patients referred to us with the presumptive diagnosis of soft tissue sarcoma (STS). METHODS: We reviewed all patients referred to us with suspected soft tissue sarcoma (STS) of the extremities or trunk over a 12-year period. RESULTS: We treated 597 patients with soft tissue tumors. Open biopsy revealed soft tissue sarcoma in 318 cases, benign mesenchymal tumor in 124 cases and isolated metastases (ISTM) from carcinomas in 98 patients; other pathologies were found in 57 patients. The primary carcinomas were lung cancer in 26 patients, breast cancer in 19 patients, renal carcinoma in 16 patients, carcinoma of the esophagus in 12 patients, colonic carcinoma in 5 patients, thyroid gland cancer in 6 patients, and in 14 patients carcinoma of unknown primary was diagnosed. CONCLUSIONS: In our collective with soft tissue tumor, 50% of the patients had the diagnosis of soft tissue sarcoma, 20% presented with a metastasis of carcinoma and 20% had a benign tumor. Referring to our results, in patients with the presumptive diagnosis of soft tissue sarcomas, soft tissue metastasis of a primary carcinoma was unexpectedly common, indicating that greater consideration should be given to this differential diagnosis.     

Oncological outcome,functional results and costs after unplanned excision of musculoskeletal soft tissue sarcoma

BackgroundTreatment of soft tissue sarcomas (STS) should only be initiated once the diagnosis is fully established. Resection of tumors of unknown nature should be avoided. Nevertheless, specialized centers continue to face numbers of unplanned excisions (UPE) in STS.AimTo compare oncologic and functional outcomes, number of surgeries, length of hospital stay and treatment costs of UPE versus planned excision (PE) in STS.MethodA retrospective single tertiary center study was performed on 201 patients. Survival, local and distant recurrence rates were compared between PE (n = 137) and UPE (n = 64). In a subgroup analysis of 60 patients, functional outcome (MSTS and TESS scores), and socio-economic impact (number of surgeries, length of hospital stay and treatment costs) in “functional planned excision” (fPE) group (n = 30) and “functional unplanned excision” (fUPE) group (n = 29) were compared.ResultsThere was no significant difference in oncological outcome between PE and UPE. In the subgroup analysis, we found a non-significant difference in functional outcome. Patients in the fUPE had significantly more surgeries (3.5 vs. 1.4; p < 0.00001) and costs of their management was 64% higher than fPE (p = 0.048). Hospital stay was longer after fUPE but not statistically significant (18.3 days vs. 11.8 days; p = 0.13).ConclusionEven though oncological and functional outcomes are comparable after PE and UPE of STS, the number of surgeries, length of hospital stay and treatment costs were higher in patients with UPE. Our data underscore the importance of specialized STS treatment centers including multidisciplinary management.     

(Neo)adjuvant treatment in localised soft tissue sarcoma: The unsolved affair

Soft tissue sarcomas (STS) are rare and heterogeneous tumours. A correct definition of STS is imperative from the very beginning of disease management, to guide the diagnostic and imaging work-up, and help to establish the prognosis on which the therapeutic strategy will be based. Over the last few years, many efforts have been made to identify characteristics that could predict disease behaviour and to enrich the therapeutic armamentarium against the advanced disease, that is still characterised by poor prognosis. Surgery remains the milestone of treatment for localised STS, whereas many uncertainties regarding the role of adjuvant and neoadjuvant treatment persist. Some controlled evidence is available, but often conflicting and insufficient to make chemotherapy (CT) a standard practice and, currently, a common and shared strategy does not exist. The biggest question concerns the prospective identification of the subgroup of patients who would benefit the most from (neo)adjuvant therapies. In light of the growing understanding of different biologies and sensitivities of the various sarcoma subtypes, the value of histology in the selection of peri-operative treatments is one of the most intriguing topics under discussion. In this perspective, a new generation of neoadjuvant trials have been planned and are currently ongoing.The aim of this review was to rekindle interest in the long-standing topic of (neo)adjuvant CT in localised STS, providing an update on its role in sarcomas' management and highlighting future directions and consequential factors needed to further improve outcomes in this disease.     

Morbidity of adjuvant brachytherapy in soft tissue sarcoma of the extremity and superficial trunk

Purpose: We have previously shown that adjuvant brachytherapy (BRT) improves local control in soft tissue sarcoma (STS) of the extremity and superficial trunk. A detailed assessment of the morbidity of this approach has not been examined. The purpose of this study was to evaluate the toxicity associated with adjuvant BRT in terms of wound complications, bone fracture, and peripheral nerve damage.

Methods and Materials: Between July 1982 and June 1992, 164 adult patients with STS of the extremity or superficial trunk were randomized intraoperatively to receive or not to receive BRT after complete resection. BRT was delivered with ¹⁹²Ir to a total dose of 42–45 Gy. The BRT and no-BRT arms were balanced with regard to age, sex, presentation (primary vs. recurrent), site, grade, size, and depth. Morbidity was assessed in terms of significant wound complication, bone fracture, and peripheral nerve damage (grade ≥ 3). The significant wound complications were defined as those wound problems requiring operative revision for coverage or threatened limb loss, persistent seroma requiring repeated aspirations and/or drainage, wound separation > 2 cm, hematoma > 25 ml, and/or purulent wound discharge. The median follow-up was 100 months.

Results: The significant wound complication rate was 24% in the BRT group and 14% in the no-BRT group, (p = 0.13). The rate of wound reoperation, however, was significantly higher in the BRT arm (10% vs. 0%; p = 0.006). Examination of other covariables that may have contributed to wound reoperation revealed the width of the excised skin (WES) to be a significant factor [1% (WES ≤ 4 cm) vs. 10% (WES > 4 cm), p = 0.02]. Bone fracture only occurred in patients receiving BRT (n = 3, 4%), although this was not statistically significant (p = 0.2). The rate of peripheral nerve damage, however, was similar in both arms (7% vs. 7%).

Conclusion: The overall morbidity associated with adjuvant BRT was not significantly higher than that with surgery alone. However, BRT and WES > 4 cm were associated with significantly higher wound reoperation rate. This has significant implications for strategies designed to maximize wound coverage in patients who receive BRT.