Recurrent Soft Tissue Sarcoma Research Articles

Intraoperative Radiotherapy with Low Energy x-Rays for Primary and Recurrent Soft-Tissue Sarcoma

Intraoperative Radiotherapy with Low Energy x-Rays for Primary and Recurrent Soft-Tissue Sarcoma

Retrospective analysis of treatment patterns among recurrent/metastatic soft tissue sarcoma patients who consulted medical oncologists in Japan

BackgroundMany new antitumor drugs to treat soft tissue sarcoma (STS) were approved in the 2010's, and the need for the management of STS patients by medical oncologists has been increasing. Clinical data about the patterns of treatment of STS patients by medical oncologists in Japan are lacking. MethodsWe retrospectively reviewed the clinical records of STS patients who consulted the Department of Medical Oncology at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research between August 2012 and March 2017. The STS patients who received any systemic chemotherapy at the Department of Medical Oncology were enrolled in the analyses. We evaluated the details of the systemic chemotherapies used: treatment regimens, drugs, and treatment settings. We focused on the treatment lines and the prognoses of salvage chemotherapy administered for recurrent and/or metastatic STS patients. ResultsAmong the 273 patients who consulted the Department of Medical Oncology, 185 patients (68%) received some systemic chemotherapy; 20 patients received chemotherapy as definitive and/or in a perioperative setting, and 171 patients in a salvage setting. The median overall survival of the 171 recurrent and/or metastatic STS patients who received salvage chemotherapy was 14.1 months (95%CI: 10.4–17.8), and the median number of salvage chemotherapy treatment lines throughout their follow-up periods was two lines (range 1–9). ConclusionAbout two-thirds of the STS patients who consulted a medical oncologist underwent chemotherapy. In the recurrent and/or metastatic settings, newly approved drugs such as pazopanib were frequently used, and the prognoses of the STS patients treated by medical oncologists were similar to those reported in recent global clinical trials. For the better management of patients with STS, medical oncologists should contribute to the management as multidisciplinary team members.

Changes in the tumor immune microenvironment in resected recurrent soft tissue sarcomas.

Little is known about how the tumor immune microenvironment (TIME) is modulated in recurrent soft tissue sarcomas (STS). We evaluated CD8+ T cells, CD20+ B cells, Foxp3+ regulatory T cells (Tregs), and programmed cell death ligand 1 (PD-L1) in 72 paired pre-recurrent (1st resected) versus post-recurrent (2nd resected) STS by immunohistochemistry. Correlations with time to recurrence and prognosis were determined. We found that CD8, PD-L1, CD20, and Foxp3-positive cell counts changed in post-recurrent STS. PD-L1-positive tumor cell and lymphocyte counts increased in post-recurrent STS, whereas CD8+ T cell counts decreased. Changes in CD8+ T cell, CD20+ B cell, and PD-L1+ lymphocyte counts were associated with the time interval between surgeries. At admission, fewer CD8+ T cells were detected in patients with relapse than in newly diagnosed patients. Furthermore, post-recurrent STS with fewer CD8+ T cells compared with pre-recurrent STS were more likely to exhibit re-recurrence. The change in CD8+ T cells was positively associated with overall survival. In multivariate analyses, a decrease in CD8+ T cell counts in post-recurrent STS was an independent unfavorable prognostic factor. The TIME differs between pre-recurrent STS and post-recurrent STS. The variation in CD8+ T cells and PD-L1 positivity may have essential roles during tumor relapse and provides a basis for determining therapeutic strategies.

Significance of HIFU in local unresectable recurrence of soft tissue sarcoma, a single-center, respective, case series in China

PurposeMultimodality treatment of soft tissue sarcoma(STS) by expert teams reportedly affords a tremendous improvement in outcome of patients. Despite advances, treatment of local unresectable recurrence remains difficult and is not standardized. We performed this retrospective study in order to assess the efficacy and safety of high-intensity focused ultrasound (HIFU) ablation in treating STS patients with local unresectable recurrence. MethodsThirty-six STS patients with local unresectable recurrence from January 2015 to December 2016 were recruited according to the inclusion criteria. Pain rating, response rate, disease control rate, local disease progression-free survival(LPFS), progression-free survival (PFS) and overall survival(OS) were used to evaluate efficacy of HIFU treatment. ResultsHIFU resulted in a significant relief in pain rating, without severe side effects. According to magnetic resonance imaging(MRI), three months after HIFU treatment, response rate was 47.3% and the local disease control rate was 80.6%. Twelve months post HIFU treatment, response rate was 38.9% and the local disease control rate was 55.6%. The median LPFS, PFS and OS time for 36 patients was 13 months, 10 months and 20 months respectively. ConclusionHIFU is a tolerated treatment modality with promising activity and safety in STS patients with local unresectable recurrence.

Abstract 1995: Low-dose eribulin suppresses lung metastasis of osteosarcoma in vitro and in vivo

Abstract Osteosarcoma is the most common malignant bone tumor among children and adolescents. The prognosis of osteosarcoma remains poor in these thirty years because the effective therapeutic option for lung metastasis has not been established. Therefore, the development of effective metastatic therapy is required. Eribulin, a new microtubule targeting agent, has been indicated for recurrent breast cancer and malignant soft tissue sarcoma. Clinical trials of eribulin showed that it elongated overall survival period rather than disease-free survival period. These results motivated us to investigate the effect of eribulin on metastasis suppression of osteosarcoma. Here, we examined the inhibitory effect of eribulin on lung metastasis and its mechanism using murine osteosarcoma metastasis model. In vivo experiments: Eribulin was intravenously injected by two administration methods, (1) high dose administration on standard schedule; 1 mg/kg q7d × 2, (2) frequent low dose administration; 0.3 mg/kg q4d × 4. Both methods sufficiently reduced circulating tumor cells in blood and inhibited lung metastasis. Method (1) also inhibited primary tumor growth, but induced severe body weight loss. Method (2) had little effect on primary tumor growth and showed little body weight loss. In vitro experiments: The IC50 concentration of eribulin for metastatic osteosarcoma cell line, LM8, was about 20 nM. Pharmacokinetics studies have shown that eribulin intravenously administered at 1 mg/kg presents with a brief high-concentration phase which surges to ≥100 nM followed by a long low-concentration phase which stabilizes at ~10 nM for one week. These two phases sandwiched the IC50 concentration of eribulin. Thus, we separately investigated that the effect of high and low eribulin concentrations on LM8. High eribulin concentrations induced cell cycle arrest and apoptosis in LM8, whereas low eribulin concentrations changed cell morphology and decreased cell migration through reducing directionality and focal adhesion turnover. Reduced peripheral localization of adenomatous polyposis coli (APC) protein by eribulin might cause these effects. In a three-dimensional collagen culture system, low eribulin concentrations inhibited tumor cell infiltration and colony formation. The anti-metastatic effects at low concentrations backed-up the results of our in vivo experiments by frequent low dose administration method. Eribulin is a potential therapeutic option for lung metastasis of osteosarcoma. Frequent low dose administration method with fewer side effects enables the combination with other chemotherapeutic agents and broadens the application of eribulin as an anti-metastatic drug for osteosarcoma. Citation Format: Kenta Watanabe, Yoshihiro Yui, Satoru Sasagawa, Kayo Suzuki, Masahiko Kanamori, Taketoshi Yasuda, Tomoatsu Kimura. Low-dose eribulin suppresses lung metastasis of osteosarcoma in vitro and in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1995.

Influence of surgical margin completeness on risk of local tumour recurrence in canine cutaneous and subcutaneous soft tissue sarcoma: A systematic review and meta-analysis.

The present peer-reviewed veterinary literature contains conflicting information regarding the impact of surgical margin completeness on risk of local tumour recurrence in canine soft tissue sarcoma (STS). This systematic review and meta-analysis was designed to answer the clinical question: "Does obtaining microscopically tumour-free surgical margins reduce risk for local tumour recurrence in canine cutaneous and subcutaneous STS?" A total of 486 citations were screened, 66 of which underwent full-text evaluation, with 10 studies representing 278 STS excisions ultimately included. Cumulatively, 16/164 (9.8%) of completely excised and 38/114 (33.3%) of incompletely excised STS recurred. Overall relative risk of 0.396 (95% confidence interval = 0.248-0.632) was calculated for local recurrence in STS excised with complete margins as compared to STS excised with incomplete margins. Risk of bias was judged to be low for all studies in terms of selection bias and detection bias but high for all studies in terms of performance bias and exclusion bias. The results of the present meta-analysis, coupled with the results of individual previous studies, strongly suggest that microscopically complete surgical margins confer a significantly reduced risk for local tumour recurrence in canine STS. Future studies ideally should adhere to standardized conducting and reporting guidelines to reduce systematic bias.

Efficacy and dosimetry prognostic factors of image guided 125I seed implantation for locally recurrent soft tissue sarcoma.

11073 Background: To observe the effect of ultrasound / CT guided radioactive 125I seed implantation in the treatment of recurrent soft tissue sarcoma and its relationship with physical dosimetry prognostic factors. Methods: The data of 37 patients with recurrent soft tissue sarcoma who received ultrasound/CT-guided 125I seed implantation from November 2005 to December 2015 were retrospectively analyzed. The local progression-free survival rate and overall survival rate were evaluated. The relationship of local progression-free survival rate and overall survival with physical dosimetric parameters was analyzed. Results: Thirty-seven patients, 20 males and 17 females, with a median age of 53 years (16-79 years), received a median radiation dose of 60 Gy (28 Gy-120 Gy). The median tumor volume was 46.8 cm3 (0.5-252.2 cm3), the median particle activity was 0.67 mCi (0.4-0.84 mCi), and the median implanted particle number was 60 (3-158). The median follow-up time was 20 months (range: 1~144 months). The median overall survival time was 20.0 months (95% CI 16.4-23.6 months). The overall survival rates of 1, 3 and 5 years were 62.2%, 34.3% and 27.7% respectively. The median local progression-free time was 63.0 months. The 1-year, 3-year and 5-year local progression-free survival rates were 68.9%, 55.0% and 47.1%, respectively. Correlation analysis showed that HI was positively correlated with total survival and local progression-free survival (P = 0.001). Multivariate analysis showed that HI ( > 0.25) was an independent prognostic factor for long overall survival (P = 0.048, HR 0.39), and D90 ( > 110 Gy) was an independent prognostic factor for long local progression-free survival (P = 0.024, HR 0.17). Conclusions: Ultrasound/CT guided 125I seed implantation is a safe and effective method for the treatment of recurrent soft tissue sarcoma with high local control rate. The HI and D90 of the postoperative plan maybe affect the therapeutic efficacy.

Copy number variations of apoptosis-regulating genes and MKI67 gene in primary and recurrent soft tissues sarcomas.

e22517 Background: Soft tissue sarcomas (STS) are relatively rare malignant tumors of mesenchymal origin, constituting about 1% of all solid human tumors. About 11% of STS cannot be classified. The relapses of STS are difficult to predict. So, the studying of molecular origin of STS remains to be an actual issue. We analyzed copy number variations (CNVs) of apoptosis-regulating genes and MKI67 gene in primary and recurrent STS. Methods: 32 patients with primary STS and 26 patients with relapses were investigated. Relative CNVs of bax, bcl2, casp3, casp8, casp9, p53, mdm2 and M kI67 were detected with the use of RT–qPCR in fresh frozen tumor and normal tissues obtained while surgical access. Relative Copy Quantitation (RCQ) was accounted with GAPDH and ACTB as reference genes. Results: The frequencies of CNVs of the studied genes in groups of primary and recurrent STS are presented in the table below. A significant change only in the group of primary STS sarcomas was observed for CNV of MDM2, whereas the amplification of the CASP3 and MKI67 genes was characteristic of recurrent sarcomas. CNVs of BAX and CASP8 were significantly more frequent in primary STS. Increased amplification of MDM2 gene, was observed only for liposarcomas among all the others STS. The literature describes amplification of chromosome 12q13-15 where MDM2 gene is localized as a diagnostic feature of liposarcoma which is consistent with our observations [Todorov SS, Kit OI Modern understanding of the morphogenetic features of liposarcomas // Archives of Pathology. 2012. T. 74. №6. p.59-61]. Conclusions: The study showed the potential role of CNV of the BAX, CASP3, CASP8 and MKI67 genes to develop an approach to predicting the course of STS and the effectiveness of the MDM2 gene amplification as an additional marker for liposarcoma molecular classification.[Table: see text]

Comparative DNA cytometry of primary and recurrent soft tissue sarcomas.

e22516 Background: Soft tissue sarcomas (STS) are aggressive tumors with a high degree of recurrence. Radical resection within healthy tissues allows to reduce the recurrence percentage to 25-30% without subsequent therapy. The literary analysis has shown that the study of various biological properties of primary and recurrentsoft tissue tumorsis being conducted. However, currently there is a lack of information to understand the reasons for STS recurrence. The goal of investigation was to reveal the distinctive features of the DNA content and cell distribution in the phases of the cell cycle of recurrent STS. Methods: DNA cytometry in the tumor tissue of 30 primary soft tissue sarcomas and 30 STS recurrences was carried out using the method of flow cytofluorometry. The tumor ploidy and cell distribution in the cell cycle phases were analyzed. Results: A number of differences in the DNA cytometric parameters of primary and recurrent STS have been revealed, they include: an increase in the proportion of aneuploid tumors in case of recurrence, the number of tumors with DNA index within the mitotic cycle, an increase in the proportion of cells in G2+M- phase of diploid and aneuploid tumors and a decrease in S- phase of aneuploid ones. It has been shown that with a G2 differentiation degree, the proportion of cells in G2+M, S- and proliferation index of recurrent STS is significantly lower than the primary parameters. An increase in the proportion of cells in G2+M- phase and a decrease in the rate of proliferation of recurrent STS, depending on the stage, are shown only in case of stage III. Conclusions: The revealed features of DNA content and cell cycle of tumor cells of soft tissue sarcomas will allow to approach to understanding of biological bases of recurrence of this malignant disease.

Feasibility of surgical salvage combined with intraoperative radiation therapy (IORT) for recurrent soft tissue sarcoma after multimodality treatment

Feasibility of surgical salvage combined with intraoperative radiation therapy (IORT) for recurrent soft tissue sarcoma after multimodality treatment

Effective palliative treatment of recurrent soft tissue sarcoma in a dog using imatinib mesylate (Gleevec<sup>®</sup>)

A 14-year-old neutered female Yorkshire terrier presented with a rapidly growing gluteal mass. There was a history of surgical resection of a mass diagnosed as a grade two soft tissue sarcoma in the same region a year earlier. The second mass was surgically excised and histopathologically diagnosed as grade two soft tissue sarcoma. A further relapse occurred six months after the second surgery. On that occasion, the dog was treated with metronomic chemotherapy consisting of cyclophosphamide and piroxicam, which failed to adequately control the disease and the mass increased 2.5-fold in size in three weeks. Imatinib treatment was started, after which there was a 62% reduction in the size of the mass. The patient has remained in partial remission for five months. To the authors’ knowledge, this is the first report on the use of imatinib to treat canine soft tissue sarcoma. Imatinib might be a useful treatment for soft tissue sarcoma that recurs after surgical resection.

A phase II study of temsirolimus and liposomal doxorubicin for patients with recurrent and refractory bone and soft tissue sarcomas

BackgroundRelapsed and refractory sarcomas continue to have poor survival rates. The cancer stem cell (CSC) theory provides a tractable explanation for the observation that recurrences occur despite dramatic responses to upfront chemotherapy. Preclinical studies demonstrated that inhibition of the mechanistic target of rapamycin (mTOR) sensitizes the CSC population to chemotherapy.MethodsHere we present the results of the Phase II portion of a Phase I/II clinical trial that aimed to overcome the chemoresistance of sarcoma CSC by combining the mTOR inhibitor temsirolimus (20 mg/m2 weekly) with the chemotherapeutic agent liposomal doxorubicin (30 mg/m2 monthly).ResultsFifteen patients with relapsed/refractory sarcoma were evaluable at this recommended Phase 2 dose level. The median progression free survival was 315 days (range 27–799). Response rate, defined as stable disease or better for 60 days, was 53%. Nine of the patients had been previously treated with doxorubicin. Therapy was well tolerated. In a small number of patients, pre- and post- treatment tumor biopsies were available for assessment of ALDH expression as a marker of CSCs and showed a correlation between response and decreased ALDH expression. We also found a correlation between biopsy-proven inhibition of mTOR and response.ConclusionsOur study adds to the literature supporting the addition of mTOR inhibition to chemotherapy agents for the treatment of sarcomas, and proposes that a mechanism by which mTOR inhibition enhances the efficacy of chemotherapy may be through sensitizing the chemoresistant CSC population. Further study, ideally with pre- and post-therapy assessment of ALDH expression in tumor cells, is warranted.Trial registration The trial was registered on clinicaltrials.gov (NCT00949325) on 30 July 2009. http://www.editorialmanager.com/csrj/default.aspx

Efficacy of radio-hyperthermo-chemotherapy as salvage therapy for recurrent or residual malignant soft tissue tumors

Background: Recurrence after wide excision or residual tumor after an unplanned excision of a malignant soft tissue sarcoma (STS) is a complex problem, due to a higher recurrence rate and poorer survival rate compared with primary resection. Regional hyperthermia was used, with the expectation that it will enhance the anti-tumor effects of chemotherapy and radiotherapy. This study aimed to assess the efficacy of neoadjuvant concomitant radiotherapy, hyperthermia, and chemotherapy (RHC) for salvage of recurrent or residual malignant STS.Methods: We identified 64 patients with recurrent or residual STS treated between 1994 and 2013. After excluding those with low-grade malignancy, with recurrent bone tumor in the soft tissues, with truncal STS, and who declined to participate, 23 patients (7 with recurrence and 16 with residual tumor) underwent RHC. The histologic diagnoses were undifferentiated pleomorphic sarcoma (n = 11), synovial sarcoma (n = 3), leiomyosarcoma and myxoid liposarcoma (n = 2 each), and other histologic types. As primary outcomes, the 5-year overall survival (OS), distant metastasis-free survival (D-MFS), and local control (LC) rates were evaluated by Kaplan-Meier analysis.Results: The median follow-up period was 112.3 months. The 5-year OS, D-MFS, and LC were 86.4%, 77.4%, and 86.7%, respectively. In the univariate analysis, tumor depth was considered as a negative prognostic factor for OS and D-MFS, and a positive margin was also a negative prognostic factor for OS, D-MFS LC with retained on Cox proportional hazards model in OS, and D-MFS.Conclusion: RHC is an effective option for salvage treatment of recurrent and residual STS.

Wound Complications After Multimodal Treatment of Soft Tissue Sarcomas

Background: Surgical removal of the tumor remains the only 1 radical treatment of patients with soft tissue sarcomas of the extremities. However, the parameters of total and disease-free survival after this type of treatment cannot be considered satisfactory. Currently the active search and introduction into clinical practice of additional impact methods that can improve the immediate and long-term results of treatment of such patients is being conducted. Aim: To evaluate the risk of the wound process complications after surgical treatment of soft tissue sarcomas using endovascular embolization and cryosurgery. Methods: We have assessed the quantity and quality of postoperative complications of wound process in 199 patients with soft tissue sarcomas and their recurrences. The study group consisted of 53 patients, who underwent radical surgery with selective preoperative endovascular embolization and intraoperative cryosurgery. The control group consisted of 146 patients who had radical surgery without any additional methods. Preoperative embolization and cryosurgery on the wound bed after tumor removal was used to prevent local recurrence of soft tissue sarcomas. Preoperative angiography with selective embolization of vessels feeding the tumor was performed 1-1.5 hours before the main surgical treatment. Cryosurgery was carried out by the method of “Olympic rings” with 3 minutes duration. The temperature of exposure was −186°C. In the course of cryosurgery we adhere to the principle of “quick freezing - an independent slow thawing”. All postoperative wounds tightly sutured with silicone drains by Redon, if necessary. Results: Complications of wound healing have been diagnosed in 15 (28.3%) patients of the main group and in 34 (23.3%) control group patients. Inflammatory-suppurative complications were observed in the remaining 8 (15.1%) patients of the main group and in 18 (12.3%) control group patients ( P > 0.05). Long lymphorrhea was observed in 6 (11.3%) patients of the main group and 11 (7.5%) control group patients. Bleeding in the postoperative period was observed in 1 (1.9%) case of main group patients and in 5 (3.4%) cases of control group. Conclusion: The additional using of selective preoperative endovascular embolization and cryosurgery is safe and does not worsen immediate results of surgical treatment of soft tissue sarcomas.

Human mesenchymal stromal cells do not promote recurrence of soft tissue sarcomas in mouse xenografts after radiation and surgery

Background. Mesenchymal stromal cells (MSCs) promote wound healing, including after radiotherapy (RT) and surgery. The use of MSCs in regenerative medicine in the context of malignancy, such as to enhance wound healing post-RT/surgery in patients with soft tissue sarcomas (STSs), requires safety validation. The aim of this study was to determine the effects of human MSCs on STS growth in vitro and local recurrence and metastasis in vivo. Methods. Human primary STS and HT-1080 fibrosarcoma lines were transduced to express luciferase/eGFP (enhanced green fluorescent protein). Sarcoma cells were co-cultured or co-injected with bone marrow–derived MSCs for growth studies. Xenograft tumor models were established with STS lines in NOD/SCID/γcnull mice. To emulate a clinical scenario, subcutaneous tumors were treated with RT/surgery prior to MSC injection into the tumor bed. Local and distant tumor recurrence was studied using histology and bioluminescence imaging. Results. MSCs did not promote STS proliferation upon co-culture in vitro, which was consistent among MSCs from different donors. Co-injection of MSCs with sarcoma cells in mice exhibited no significant tumor-stimulating effect, compared with control mice injected with sarcoma cells alone. MSC administration after RT/surgery had no effect on local recurrence or metastasis of STS. Discussion. These studies are important for the establishment of a safety profile for MSC administration in patients with STS. Our data suggest that MSCs are safe in STS management after standard of care RT/surgery, which can be further investigated in early-phase clinical trials to also determine the efficacy of MSCs in reducing morbidity and to mitigate wound complications in these patients.

Chronic active hepatitis induced by Pazopanib mimicking hypervascular liver metastases in a patient with recurrent soft tissue sarcoma: A case report.

Pazopanib is the first multitargeted tyrosine-kinase inhibitor approved for the treatment of patients with advanced non-adipocytic soft tissue sarcoma (STS). It has been demonstrated to improve progression-free survival without impairing health-associated quality of life. However, Pazopanib is associated with several adverse side effects associated with inhibition of the vascular endothelial growth factor receptor. These include hepatotoxicity, as manifested by abnormal liver function tests. To the best of our knowledge, the current study presents the first case of a patient with recurrent STS who developed biopsy proven Pazopanib-induced chronic active hepatitis and whose previous computed tomography examination demonstrated multiple hypervascular liver lesions. These lesions were indistinguishable from metastases and to the best of our knowledge, have not been described previously. These lesions therefore appear to be a novel finding of Pazopanib-induced chronic active hepatitis. It is crucial to be aware of this unusual finding within a clinical setting, to avoid overstaging and early discontinuation of effective treatment.

Use of 18F-FDG-PET/CT for Retroperitoneal/Intra-Abdominal Soft Tissue Sarcomas.

Rationale To assess the diagnostic value of 18F-FDG-PET/CT for different retroperitoneal soft tissue sarcomas (STS) and other similar tumors. To analyze the predictive value of 18F-FDG-PET/CT for histological grade and main prognostic factors. Methods 195 patients with 44 different diseases have been included. Relationship between SUVmax, Clinical, pathological, and prognostic information has been analyzed. Results Malignant tumors do not show higher SUVmax than benign ones (P=0.443). We divided all 44 different diseases into two groups; SUVmax of group 1 is significantly higher than group 2 (P ≤ 0.001). The ROC curve suggests 4.35 is the cutoff value to distinguish groups 1 and 2 (sensitivity = 0.789; specificity = 0.736). SUVmax correlates with Ki-67 index, mitotic count, vascular resection, histological grade, and recurrent STS without considering pathological diagnosis (P=0.001, P=0.012, P=0.002, P ≤ 0.001, and P=0.037, resp.). Conclusion 18F-FDG-PET/CT cannot simply distinguish malignant and benign tumors in retroperitoneal/intra-abdominal cavity; however, the SUVmax of malignant tumors, inflammatory pseudotumor, and PPGL group is higher than the SUVmax of benign tumors, lymph node metastasis, hematoma, and low malignant STS group. Guidance of “SUVmax location” may be helpful for biopsy and pathology dissection.

Efficacy and clinical prognostic factors of image-guided 125I seed implantation for locally recurrent soft tissue sarcoma

Objective To evaluate the outcomes and prognostic factors of image-guided 125I seed implantation for locally recurrent soft tissue sarcoma(RSTS). Methods A total of 60 patients with RSTS who received image-guided 125I seed implantation in Peking University Third Hospital, from September 2002 to December 2015, were retrospectively analyzed. The enrollment criteria: KPS > 60 points, refused or could not tolerate surgery or radiotherapy, the expecting survival time >3 months, relapsed after multiple treatment of soft tissue sarcoma, and underwent CT or ultrasound guided 125I seed implantation treatment. In all, the median activity of seeds was 25.9×106 Bq (range, 11.1×106-29.6×106 Bq), median number of implanted seeds was 58 (range, 3-133), and the median D90 was 120 Gy (range, 36.50-460.97 Gy). The local progression-free survival (LPFS) and overall survival (OS) were calculated using the Kaplan-Meier method . The log-rank test and Cox regression model were used for the univariate and multivariate analyses. Results The median follow-up was 18.75 months (range, 1-146). The median OS was 18.5 months (95% CI 13.1-23.9). The 1-, 3- and 5-year OS rate were 63.3%, 33.0% and 29.5%, respectively. The 1-, 3- and 5-year LPFS rate were 72.5%, 63.7% and 59.7%, respectively. The general rate of pain relieving was 100% (6/6). 8.3% (5/60) presented grade Ⅳ skin toxicity. No fatal complications ocurred. The univariate analysis suggested that tumor size, tumor volume, KPS score, D90 were prognostic factors of OS and LPFS. The multivariate analysis demonstrated that previous chemotherapy history and distant metastases were independent prognostic factors of survival. Conclusions Image-guided 125I seed implantation for recurrent soft tissue sarcoma is a safe treatment option with high efficacy and low morbidity. Tumor size and D90 were the prognostic factors of OS and LPFS. Key words: Recurrence; Soft tissue sarcoma; 125I seed implantation; Prognosis

Efficacy and Clinical Prognostic Factors of Image-guided 125I Seed Implantation for Locally Recurrent Soft Tissue Sarcoma

Efficacy and Clinical Prognostic Factors of Image-guided 125I Seed Implantation for Locally Recurrent Soft Tissue Sarcoma

DNA-cytometric characteristics of recurrent soft tissue sarcomas

Aim. To determine the content of deoxyribonucleic acid (DNA) and distribution of cells in mitotic phases in patients with recurrent soft tissue sarcomas for the assessment of malignancy of the process. Methods. Tumor tissues of patients with recurrent soft tissue sarcomas were studied. Research methods included histological, DNA-cytometric and statistical methods. Results. Proliferative activity and proliferative index of recurrent sarcomas differed depending on the tumor grade and stage. Differences in the number of diploid, aneuploid and polyploid cells were determined in each group and between the groups depending on the cell cycle phases. Cell cycle parameters were as following: 100% of G1 (well-differentiated) cancer were diploid, as well as 33.3% of G2 (moderately differentiated) and 15% of G3 (poorly differentiated) tumors. Aneuploid tumors prevailed in G2 and G3, the ratio of which was 66.7 and 85%, respectively. The analysis of kinetic parameters of the cell cycle allowed establishing a decrease in the number of cells in G1/G0 phase of the cell cycle from G1 to G3, which was accompanied by a statistically significant increase in the proportion of cells in S-phase (p ˂0.05). Conclusion. The DNA-cytometric study of cell cycle parameters showed high biological potential of recurrent soft tissue sarcomas, which was determined by two indices - the proportion of cells in G2+M-phase and the cell loss factor; 100% of well-differentiated (G1) tumors, 33.3% of moderately differentiated (G2) and 15% of poorly differentiated (G3) tumors were diploid; aneuploid tumors prevailed in G2 and G3.