Abdominal soft tissue sarcoma: a multicenter retrospective study

Background  

Soft tissue sarcomas (STS) are rare mesenchymal neoplasms with a variety of histological subtypes. However, in Japan, data on the clinical characteristics and prognostic profiles of these tumors are lacking. The purpose of the present study was to clarify the clinical features and outcomes of Japanese patients with retroperitoneal and abdominal STS.     

Paclitaxel in patients with advanced angiosarcomas of soft tissue: a retrospective study of the EORTC soft tissue and bone sarcoma group

RationaleAngiosarcomas of soft tissue represent a heterogenous group of rare sarcomas with specific clinical behaviour and risk factors. Paclitaxel appears to induce tumour control in a higher proportion of patients with angiosarcoma, as compared to other sarcomas. The objective of this retrospective study was to assess the anti-tumour activity of this compound in a multicentre setting.MethodClinical data from patients with angiosarcomas of soft tissue treated with single agent paclitaxel were collected from the centres of the soft tissue and bone sarcoma group of EORTC, using a standardised data collection form. Paclitaxel could be given every three weeks, or weekly. Statistical analysis was performed using SAS software.ResultsData from 32 patients were collected from 10 centres. There were 17 males, 15 females, with a median age of 60.4 years (range, 25–91). Primary angiosarcomas were located in scalp and face in 8 patients (25%) and at other primary sites in 24 patients (75%). All patients had intermediate (n = 13) or high grade (n = 19) primary tumours. Thirteen (40%) patients had been pretreated with doxorubicin-based first-line-chemotherapy and three of them (9%) had also received second-line chemotherapy with ifosfamide. Eleven (34%) patients had been irradiated before as treatment for angiosarcoma. In 8 (25%) patients, the angiosarcoma occurred at sites of prior radiation therapy for other malignancies. The response rate was 62% (21/32) in the whole series, 75% (6/8) in scalp angiosarcomas and 58% (14/24) in other primary sites. The median time to progression was 7.6 months (range, 1–42) for the whole group. For the face/scalp group it was 9.5 months, and for patients with angiosarcomas at other sites it was 7.0 months, respectively.ConclusionPaclitaxel was found to be an active agent in angiosarcoma of soft tissue in this retrospective analysis. These results need to be confirmed in a prospective randomised phase II study.     

Current results of brachytherapy for soft tissue sarcoma

Perioperative brachytherapy results in a better local control rate than surgery alone for extremity soft tissue sarcoma. Brachytherapy enables the delivery of a high radiation dose to a limited volume of tissue, allows the reduction of radiation treatment time, enables direct visualization of the tumor bed and surrounding critical structures, and costs less than external beam radiotherapy. The literature seems to regard the effectiveness of brachytherapy as comparable to that of external beam radiotherapy, and the side effect profile is acceptable. Traditional low-dose-rate brachytherapy methods require extended periods of patient isolation, but recent technologic advances may obviate this necessity. Newer high-dose-rate (HDR) brachytherapy delivery methods allow for the fractionation of radiation delivery and outpatient treatment in some cases. Furthermore, with HDR brachytherapy, the radiation dose distribution can be tailored around critical anatomic structures. Although the application of HDR brachytherapy to soft tissue sarcoma is relatively new, it seems to result in a satisfactory local control rate and may replace traditional low-dose-rate techniques.     

Local recurrence of soft tissue sarcoma following brachytherapy

Twenty-five patients with soft tissue sarcomas were treated with Ir192 implants following wide local excision at our institution between 1982 and 1987. External beam radiotherapy was given in addition to the implant in a majority of patients. The median follow-up in these 25 patients is 36 months (12 to 75 months). Twenty patients have had no evidence of local recurrence following their primary treatment (FFR = 80%). A multivariate analysis using stepwise logistic regression was used to predict failure in 3 years or less. Potential predictors examined included age, sex, tumor location, primary versus recurrent disease, grade, histology, surgical margins, implant only versus implant plus external beam, and a ratio of the volume of tissue which received 65 Gy (TV65) to the tumor volume (TV), that is (TV65/TV). The single variable which was significantly associated with local failure by 3 years was a TV65/TV of less than one. Once this variable was entered into the analysis, no other factor proved statistically significant. Our data suggest that when attempting local control of soft tissue sarcomas with brachytherapy, the volume of tissue receiving 65 Gy (TV65) from both implant and external beam must exceed the volume of the excised lesion (TV). Since the volume of a tumor can be readily determined prior to surgical excision either by CT or MRI scanning, pre-planning of the implant volume could potentially reduce the rate of local failure.     

High-dose-rate brachytherapy for soft tissue sarcoma in children: a single institution experience

Background

The shape of the dose-response curve at low doses differs from the linear quadratic model. The effect of a radio-adaptive response is the centre of many studies and well known inspite that the clinical applications are still rarely considered.

Methods

We studied the effect of a low-dose pre-irradiation (0.03 Gy – 0.1 Gy) alone or followed by a 2.0 Gy challenging dose 4 h later on the survival of the HT29 cell line (human colorectal cancer cells) and on the GM637 cell line (human fibroblasts).

Results

0.03 Gy given alone did not have a significant effect on both cell lines, the other low doses alone significantly reduced the cell survival. Applied 4 h before the 2.0 Gy fraction, 0.03 Gy led to a significant induced radioresistance in GM637 cells, but not in HT29 cells, and 0.05 Gy led to a significant hyperradiosensitivity in HT29 cells, but not in GM637 cells.

Conclusion

A pre-irradiation with 0.03 Gy can protect normal fibroblasts, but not colorectal cancer cells, from damage induced by an irradiation of 2.0 Gy and the application of 0.05 Gy prior to the 2.0 Gy fraction can enhance the cell killing of colorectal cancer cells while not additionally damaging normal fibroblasts. If these findings prove to be true in vivo as well this may optimize the balance between local tumour control and injury to normal tissue in modern radiotherapy.     

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．．     

Long-term outcome after local recurrence of soft tissue sarcoma: a retrospective analysis of factors predictive of survival in 135 patients with locally recurrent soft tissue sarcoma

Background:

The aim of this study was to identify prognostic indicators of survival in patients with locally recurrent soft tissue sarcoma (STS) through a long-term follow-up.

Methods:

We retrospectively assessed the relationship between post-recurrence survival (PRS) and potential prognostic factors in 135 patients who had experienced local recurrence, which was suitable for further surgical treatment. The median follow-up time after initial recurrence was 12.3 years (95% confidence interval (CI): 10.4–14.2 years).

Results:

The 5-year estimate of the PRS rate was 53.1% (95% CI: 44.3–61.2%) for the entire series. Patients with negative margins after the final surgery experienced improved survival compared with patients with positive margins (5-year survival: 46.7% (35.2–57.5%) vs 35.5% (23.4–47.8%); P=0.01). In a multivariate analysis, the significant prognostic indicators for PRS were histologic grade, tumour site, time to initial recurrence, the number of recurrences and the surgical margin status attained at the last resection.

Conclusions:

Complete surgical resection with microscopically clear margins is desirable in patients with locally recurrent STS. However, when achieving clear surgical margins will require major functional impairment of the extremity, a radical surgical approach should be weighed for the patient in each case.     

A retrospective cohort study of treatment patterns among patients with metastatic soft tissue sarcoma in the US

Background

Since treatment patterns in metastatic soft tissue sarcoma (mSTS) have not been studied subsequent to US approval of pazopanib in 2012, this study sought to examine mSTS treatment patterns by line of therapy, including regimen and duration of therapy.

Methods

This retrospective study employed administrative claims from a large US health plan from 1/2006–9/2015. Adult mSTS patients were required to have an NCCN-recommended therapy and be continuously enrolled in the health plan during the study period. The most frequent regimens for distinct lines of therapy (LOT) were assessed. Sensitivity analyses evaluated changes to study findings using two alternate medical and pharmacy claims diagnostic algorithms to define the STS study population.

Results

Among 555 patients with mSTS, mean age was 59 years and 54% were male. During the study period, 41% of patients initiated ≥ 2 LOTs; 16% had ≥ 3 LOTs and 5% had ≥ 4 LOTs. Docetaxel + gemcitabine was most common in LOT1, pazopanib in LOT2 and LOT3, and doxorubicin in LOT4. The five most common LOT1 regimens represented 53% of patients; among the remaining 47%, the most common regimen represented < 6% of patients. Among patients with pazopanib in LOT2 and LOT3, the most common prior regimen was docetaxel + gemcitabine (47% and 30% respectively). Kaplan–Meier estimation of median treatment duration overall for LOT1 was 3.5 months, while for LOT2 and LOT3, median treatment duration was 2.9 and 3.3 months, respectively. For both sensitivity analyses, patient demographic and clinical characteristics were similar to the original study population, and the five most frequently used regimens in LOT1 and LOT2 were similar among the three populations regardless of the population selection criteria employed.

Conclusion

Choice of regimen by LOT among patients with mSTS is varied; < 65% of patients in any LOT received the five most common regimens. Pazopanib, the only approved targeted therapy, is primarily used in second and later lines of therapy and is mostly given post docetaxel + gemcitabine.

     

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.     

Flap reconstruction and interstitial brachytherapy in nonextremity soft tissue sarcoma

Radiotherapy is an integral component of management of high-grade soft tissue sarcomas. Interstitial brachytherapy is used to deliver a boost or radical dose with several advantages over external beam radiotherapy. There has always been a concern to use brachytherapy with flap reconstruction of skin defects after wide excision. We preset our initial experience with interstitial brachytherapy in two patients of recurrent high-grade non-extremity sarcomas treated with surgical excision and soft tissue reconstruction of surgical defect.     

Re-resection with brachytherapy for locally recurrent soft tissue sarcoma arising in a previously radiated field

PURPOSE: The use of further radiotherapy among patients with soft tissue sarcoma that recurs in a previously irradiated area is controversial. Presented is a review of our 7-year experience with brachytherapy for recurrent soft tissue sarcoma. METHODS: A retrospective review was performed of 26 patients who underwent perioperative brachytherapy between 1990 and 1997 for recurrent soft tissue sarcoma. In all cases, the sarcoma recurred within a previously irradiated field. After-loading brachytherapy catheters were placed at the time of surgical extirpation of the sarcoma within a single-plane implant by use of 1-cm intercatheter spacing. Insertion of the radioactive 192Ir wire was delayed until the fifth to seventh postoperative day to allow initial wound healing. The prescribed dose rate for the 192Ir wire ranged between 50 and 80 cGy an hour, and the dose was specified at 0.5 cm from the plane of the implant. The anatomic locations treated included lower extremity (N = 10), upper extremity (N = 7), trunk (N = 7), and head and neck (N = 2). RESULTS: Total tumor extirpation, confirmed by negative frozen section margins, was accomplished in all cases. The mean dose of external-beam irradiation received before brachytherapy was 55.6 Gy +/- 1.8 Gy (range, 30.0 to 70.3 Gy). The mean dose of radiation prescribed at the implant procedure was 47.2 Gy +/- 1.6 Gy (range, 11.0 to 50.0 Gy). A tissue transfer flap was placed over the bed of resection in 13 cases. Complications occurred in five patients including, three with wound breakdown, one with osteonecrosis, and with neuralgia. Operative intervention was required in four of the five patients with complications; each of the patients requiring operative intervention for wound-related complications had undergone primary wound closure without tissue transfer. Recurrence of disease occurred in 13 patients: nine local and four distant metastases. The median follow-up was 16 months (range, 2 to 73 months). The 5-year local recurrence-free, distant recurrence-free, disease-free, and overall survival rates after brachytherapy were 52%, 75%, 33%, and 52%, respectively. CONCLUSION: Re-irradiation of recurrent soft tissue sarcoma by brachytherapy in conjunction with resection can be performed with acceptable complication rates. Local control can be achieved for the majority of patients who would otherwise require more radical surgical procedures.     

术中置管联合高剂量率近距离放疗治疗11例软组织肉瘤

目的：观察术中置管联合高剂量率近距离放疗软组织肉瘤的毒副作用及近期疗效.方法：对11例软组织肉瘤应用高剂量率近距离放疗进行治疗.术中广泛切除肿瘤后,在瘤床放置后装管.术后第3至5天开始高剂量近距离放疗,每次剂量为200cGy,每天2次,连续5天,待伤口愈合后,再追加外照射40～50 Gy.结果：10例患者无局部复发,1例局部复发,其中1例因远处转移而死亡.各例均无明显毒副反应.结论：高剂量率近距离放疗治疗软组织肉瘤是安全易行的,并取得较好的局部控制率.在治疗软组织肉瘤方面将有可能显示出良好的应用前景.     

T-regulatory cells predict clinical outcome in soft tissue sarcoma patients: a clinico-pathological study

Background Soft tissue sarcomas (STS) are generally considered non-immunogenic, although specific subtypes respond to immunotherapy. Antitumour response within the tumour microenvironment relies on a balance between inhibitory and activating signals for tumour-infiltrating lymphocytes (TILs). This study analysed TILs and immune checkpoint molecules in STS, and assessed their prognostic impact regarding local recurrence (LR), distant metastasis (DM), and overall survival (OS).Methods One-hundred and ninety-two surgically treated STS patients (median age: 63.5 years; 103 males [53.6%]) were retrospectively included. Tissue microarrays were constructed, immunohistochemistry for PD-1, PD-L1, FOXP3, CD3, CD4, and CD8 performed, and staining assessed with multispectral imaging. TIL phenotype abundance and immune checkpoint markers were correlated with clinical and outcome parameters (LR, DM, and OS).Results Significant differences between histology and all immune checkpoint markers except for FOXP3+ and CD3−PD-L1+ cell subpopulations were found. Higher levels of PD-L1, PD-1, and any TIL phenotype were found in myxofibrosarcoma as compared to leiomyosarcoma (all p < 0.05). The presence of regulatory T cells (Tregs) was associated with increased LR risk (p = 0.006), irrespective of margins. Other TILs or immune checkpoint markers had no significant impact on outcome parameters.Conclusions TIL and immune checkpoint marker levels are most abundant in myxofibrosarcoma. High Treg levels are independently associated with increased LR risk, irrespective of margins.Subject terms: Tumour biomarkers, Prognostic markers     

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.     

Imaging evaluation of patients with soft tissue sarcoma

Imaging provides the clinician with crucial information in the diagnosis, staging, treatment planning, treatment evaluation, and post-treatment assessment of patients with soft tissue sarcoma. MRI, including contrast-enhanced sequences, usually is preferred for evaluating the primary site in extremity sarcomas and lesions of the head and neck. CT generally is preferred for imaging of the chest, abdomen, and pelvis, either in the evaluation of the primary site in those regions or for identifying metastatic disease. The experienced radiologist often can suggest a specific diagnosis or narrow differential diagnosis from the imaging characteristics, particularly with MRI. It is imperative that imaging be performed in a manner specific for the evaluation of soft tissue masses, and before biopsy or surgery, to provide the most accurate preoperative assessment and treatment planning [56, 57].     

Amputation for extremity soft tissue sarcoma does not increase overall survival: A retrospective cohort study

To determine if amputation increases survival when compared to limb salvage surgery in patients with a soft tissue sarcoma (STS) of the extremity when there is often a misconception among physicians and patients that ablative surgery eliminates local recurrence and increases overall survival. This retrospective cohort study assessed 278 patients with STS and compared 18 patients who had undergone amputations for soft tissue sarcomas of the extremities to a comparative cohort of 260 patients who underwent limb salvage surgery during the same time period. Our limb salvage surgery (LSS) rate was 94% overall for soft tissue sarcomas with a median follow-up of 3.1 years. Patients undergoing amputations either had tumors that involved a critical neurovascular bundle (in particular nerve rather than vessel resection was more responsible for a decision toward ablation), or underlying bone or had neoplasms whose large size would require such an enormous resection that a functional limb would not remain. In comparing prognostic effects, mainly death due to sarcoma, distant metastasis and local recurrence, it was found that there was no statistically significant difference between patients undergoing amputation to those undergoing limb salvage surgery (p > 0.05). While amputations do not increase overall survival in soft tissue sarcomas of the extremity as compared to LSS, they are still a valuable option in a surgeon's arsenal. In particular, amputations can provide improved local control and symptomatic treatment in patients who might not be candidates for limb salvage surgery.     

介入化疗与保肢手术治疗软组织肉瘤

目的研究术前动脉介入化疗与手术治疗肢体软组织肉瘤。方法21例肢体软组织肉瘤，其中13例(62％)术前影像学显示肿瘤邻近大血管或骨骼侵犯，采用股动脉及肱动脉插管，化疗2—3周后，施行肿瘤切除及保留肢体功能的手术。结果介入化疗后病理检查，肿瘤有不同程度的坏死，体积缩小，周围水肿浸润带减少，肿瘤与邻近组织术中易分离，术后随访6—62个月，患肢功能基本正常。结论对四肢软组织肉瘤侵犯大血管、骨骼者，术前动脉介入化疗可提高切除率，降低局部复发及保存患肢。     

Phase II study of daily oral perifosine in patients with advanced soft tissue sarcoma

BACKGROUND: A multicenter Phase II study was performed to evaluate the clinical activity of an initial loading (150 mg every 6 hours x 4 doses) dose followed by continuous daily oral dosing (100 mg/day) of perifosine in patients with advanced soft tissue sarcomas (STSs). METHODS: Patients with measurable metastatic STS received perifosine as first-, second-, or third-line treatment and underwent disease assessment every 8 weeks until disease progression, excessive toxicity, or patient refusal. RESULTS: Twenty-three patients received 66 cycles (1 cycle = 4 weeks) of perifosine. One partial response of 9 months duration was observed. The overall 3 and 6 month progression-free survival was 22% and 9%. NCI CTC (v2.0) Grade 1 to 2 gastrointestinal toxicity or fatigue were the most common (>50% of subjects) toxicities observed. The steady-state plasma perifosine levels (Css) were similar to prior experience (mean 6 microg/mL). Patients with Css levels >6 microg/mL appeared more likely to remain on study past 2 months than those with levels <6 microg/mL. CONCLUSIONS: Despite not achieving the primary objective of > or =40% 6-month progression-free survival rate, optimism remains for this agent in STS patients. Prolonged responses in heavily pretreated STS patients continue to be observed with perifosine treatment. Continued assessment of perifosine in STS appears warranted, with special attention to specific histologies or tumor characteristics that might identify a more sensitive population and achieving perifosine Css levels >6 microg/mL.