Recurrent Soft Tissue Sarcoma Research Articles

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.

Hand-foot skin reaction predicts treatment outcome of pazopanib in patients with metastatic soft tissue sarcoma: A multicenter study in the Asian population.

Pazopanib is a multitargeted tyrosine kinase inhibitor used as a standard treatment for chemotherapy-refractory recurrent or metastatic soft tissue sarcoma. This study aimed to evaluate the efficacy and safety of pazopanib for treatment of metastatic soft tissue sarcoma in the Asian population. Fifty patients with chemotherapy-refractory recurrent or metastatic soft tissue sarcoma, who had received pazopanib treatment between 2015 and 2016 were enrolled. We reviewed patients' clinical characteristics and studied survival outcomes following pazopanib treatment. Median follow-up was 5.7 months. Seven patients were still on pazopanib by the end of this study and the disease had progressed in the other 43 patients, leading to 23 deaths. We found that despite treatment more than half the patients experienced disease progression (56% vs 14% partial response and 30% stable disease). The median progression-free survival and overall survival was 3.1 and 11.0 months, respectively. Multivariate analysis identified good Eastern Cooperative Oncology Group performance status (0 or 1) and occurrence of hand-foot skin reaction as independent factors associated with better outcome. Hand-foot skin reaction was 32% in our cohort and the median onset time was 4 (1.00-8.29) weeks. It had dose-dependent effect by clinical observation. Our study showed that the incidence rate of hand-foot skin reaction in Taiwan is higher than western population, and it is an independent predictive factor for better treatment outcomes.

Local recurrence of soft-tissue sarcoma: issues in imaging surveillance strategy.

Soft-tissue sarcomas pose diagnostic and therapeutic challenges to physicians, owing to the large number of subtypes, aggressive tumor biology, lack of consensus on management, and controversy surrounding interval and duration of surveillance scans. Advances in multidisciplinary management have improved the care of sarcoma patients, but controversy remains regarding strategies for surveillance following definitive local control. This review provides an updated, comprehensive overview of the current understanding of the risk of local recurrence of soft-tissue sarcoma, by examining the literature based on features such as histological type and grade, tumor size, and resection margin status, with the aim of helping clinicians, surgeons, and radiologists to develop a tailored approach to local imaging surveillance.

Some immunohistochemical parameters in primary and recurrent soft tissue sarcomas.

e23533Background: The purpose of the study was to reveal some immunohistochemical parameters in primary and recurrent soft tissue sarcomas. Methods: The study included patients with primary (n = 30...

EP-1628: Radiotherapy for high grade late recurrent soft tissue sarcomas: follow up and outcomes

EP-1628: Radiotherapy for high grade late recurrent soft tissue sarcomas: follow up and outcomes

Hepatoprotective effect of N-acetylcysteine in trabectedin-induced liver toxicity in patients with advanced soft tissue sarcoma.

Trabectedin is one of the few active agents in soft tissue sarcoma (STS) but hepatotoxicity is frequent and represents a dose-limiting factor. Protective strategies aiming at counteracting this important side effect have a crucial clinical impact. Due to its antioxidant properties, N-acetylcysteine (NAC) has a recognized hepatoprotective effect and this provides the rationale for testing NAC in the management of trabectedin-induced hepatotoxicity. Patients with recurrent or metastatic soft tissue sarcoma, consecutively observed at our institution, who were considered eligible to trabectedin, received concomitant NAC if they had impaired hepatic or renal function at baseline or developed hepatotoxicity during treatment. The study aim was to retrospectively explore trabectedin administration in terms of number of cycles, mean dose, and dose intensity (DI) in patients who received NAC as compared with those who did not. Secondary end points were progression-free survival (PFS) and overall survival (OS). A total number of 18 patients were enrolled in this study. Nine received NAC and nine did not. The median number of administered trabectedin cycles, mean trabectedin dose/cycles, and median DI was comparable in the two groups (p = 0.450, p = 0.534, and p = 0.450, respectively). The PFS and OS curves overlapped. This explorative study suggests that NAC can have a hepatoprotective activity in patients receiving trabectedin allowing to maintain an adequate dose intensity and continuative administration in patients with impaired liver and renal function or developing treatment-induced hepatotoxicity. A prospective randomized trial is warranted.

What Is the Success of Repeat Surgical Treatment of a Local Recurrence After Initial Wide Resection of Soft Tissue Sarcomas?

Treatment for patients with locally recurrent soft tissue sarcomas after wide resection is challenging, and few studies have examined the results of treating these patients. In treatment of recurrent tumors, it has been reported that positive margins are correlated to local rerecurrence, but the relationship between surgical margin and survival remains controversial and risk factors for local recurrences after wide resection of soft tissue sarcomas are not well established. This study examined clinical outcomes and factors associated with survival and local rerecurrence in patients with local recurrence after initial surgical treatment who underwent another resection with a goal of negative margins. The purpose of this study was to determine (1) oncologic outcomes (survival rates and local rerecurrence-free rates) of surgical treatment for patients with local recurrence after wide resection; (2) whether factors associated with survival and local rerecurrence-free rates can be determined; and (3) the proportion of patients treated by amputation at final followup. Between 1992 and 2013, we treated 530 patients with soft tissue sarcoma without metastasis. Of those, 26 (5%) were lost before 3 years of followup but were not known to have died. Of the remainder, 59 have had a local recurrence. Of those with a local recurrence, 34 (58%) were treated with wide resection, whereas 25 (42%) were treated with nonsurgical treatment including chemotherapy and radiotherapy. During that period, our general indications for wide resection were patients (1) without distant metastasis; or (2) without distant lymph node metastasis, and contraindications were distant organ metastasis and/or distant lymph node metastasis. Of those treated with wide resection, 30 (88%) were available for followup. We conducted a retrospective analysis of these 30 patients with local recurrence (17 men, 13 women) who had previously undergone wide resection. Patient followup ranged from 1 to 12 years (median, 5 years). Survivorship (including overall survival and survival free from repeat recurrence) was ascertained by the Kaplan-Meier method. Factors associated with survival were evaluated by the log-rank test. Amputations were performed when limb-sparing surgery was deemed unsuitable because of extensive involvement of the limb by tumor, including invasion of multiple muscle compartments and neurovascular components. Survivorship free from amputation was ascertained by the Kaplan-Meier method. Overall 5- and 10-year Kaplan-Meier survival rates after resection were 70% (95% confidence interval [CI], 50%-91%) and 44% (95% CI, 12%-76%), respectively, and 12 patients (40%) developed distant metastases after the second operation. Ten patients (33%) had additional local recurrences, and overall 5- and 10-year local rerecurrence-free rates were 66% (95% CI, 48%-85%) and 50% (95% CI, 18%-81%), respectively. A positive margin was associated with further recurrence (5-year local rerecurrence-free rates of positive margin: 20% [95% CI, 0%-52%], negative margin: 89% [95% CI, 74%-100%], p < 0.01) and with survival (5-year survival rates of positive margin: 36% [95% CI, 0%-75%], negative margin: 91% [95% CI, 74%-100%], p < 0.01). The survival rate was lower in patients with recurrence developing after 2 years (5-year survival rates of within 2 years: 46% [95% CI, 2%-90%], after 2 years: 83% [95% CI, 62%-100%], p = 0.01). The overall 5- and 10-year amputation-free rates were 86% (95% CI, 74%-99%) and 81% (95% CI, 67%-96%), respectively. A surgical procedure with negative margins appears to be important for reducing the likelihood of local recurrences and improving survival of patients with rerecurrence after wide resection of soft tissue sarcomas. Although these findings need to be confirmed in larger studies, it appears that when tumor recurrence is evident within 2 years from the primary surgery, it is associated with a poor prognosis. Local recurrence within 2 years after wide resection may also be an indicator of aggressive tumor biology. Level IV, therapeutic study.

Aggressive Surgical Approach for Treatment of Primary and Recurrent Retroperitoneal Soft Tissue Sarcoma

To analyze treatment and survival in a series of resected patients with primary or recurrent retroperitoneal sarcoma (RPS) treated and prospectively followed at a single institution. Between July 1994 and December 2015, 89 patients (36 M, 53 F; mean age 60years, range 25-79) were evaluated. For the purpose of analysis, complete resection was defined as removal of gross tumor with histologically confirmed clear resection margins. Eighty-three out of the 89 patients (93%), 46 of whom affected by primary RPS, and 37 by recurrent RPS, underwent surgical exploration. Sixty-two had a grossly and microscopically complete resection. Fifty-three out of 83 patients (64%) underwent removal of contiguous intra-abdominal organs. Preoperative mortality was nil and significant preoperative complications occurred in six cases only (7%). High-grade tumor pointed out to be a significant variable for a worse survival in all 83 patients amenable to undergo surgical resection (57% 5years survival for low grade vs 14% for high grade; P = 0.0004). Among completely resected patients, only histologic grade clearly affected disease-free survival (72% 5years survival for low grade vs 50% for high grade; P = 0.04), while the role of preoperative blood transfusions (67% 5years survival for non-transfused patients vs 29% for transfused patients; P = 0.05) has to be evaluated in connection to patient complexity. Histological grade and recurrence are the most valuable prognostic predictors; in this clinical subset, an aggressive surgical approach in both primary and recurrent RPS is associated with a best long-term survival and disease-free survival.

Salvage Carbon Ion Radiation Therapy for Locally Recurrent or Radiation-Induced Second Primary Sarcoma of the Head and Neck.

Purpose: Salvage radiation therapy (RT) is a potentially curative treatment option for head and neck sarcomas (HNS) that did not respond to previous treatment(s). We report the first clinical experience of carbon ion radiotherapy (CIRT) for salvage treatment of locally recurrent (LR) or RT-induced secondary HNS after surgery and/or radiotherapy.Methods and Materials: A retrospective analysis of the ongoing prospective data registries from the Shanghai Proton and Heavy Ion Center was conducted. Patients with LR-HNS who underwent surgery and/or RT and those with RT-induced second primary HNS were included. Acute and late toxicities were evaluated using the Common Terminology Criteria for Adverse Events version 4.0 and the Radiation Therapy Oncology Group late radiation toxicity scoring system, respectively. The actuarial 12-month local progression-free and overall survival rates (LPFS and OS) were calculated using the Kaplan-Meier method.Results: Between 10/2015 and 7/2017, 19 consecutive and non-selected patients with LR-HNS or RT-induced secondary HNS received definitive doses of CIRT delivered with pencil beam scanning technology for salvage. Six patients had locally recurrent soft-tissue sarcoma, and another 6 had chondrosarcoma. Among these 12 patients, 4 had received one prior course of RT. Seven additional patients had an RT-induced second primary soft tissue sarcoma (STS)/osteosarcoma after RT. The median time between the completion of initial treatment (either surgery only or surgery followed by adjuvant RT) and salvage CIRT was 30.6 months.The median follow-up time was 13.1 (range 1.6-41.1) months. All patients except one (for re-irradiation) completed the planned CIRT for salvage. The median dose of salvage CIRT was 60 GyE. Three patients developed local progression, and another 3 developed distant metastasis after salvage CIRT. Deaths occurred (3 patients) only in patients with radiation-induced second primary sarcoma at the time of analysis. The actuarial 12-month LPFS, DMFS and OS rates were 74.6%, 82.6% and 86.5%, respectively.Two patients irradiated for a second primary sarcoma had Grade 4 bleeding during CIRT, including one who experienced the rupture of an optic artery aneurysm unrelated to his disease or the salvage treatment. No patient had Grade 5 toxicity during treatment. Except for one patient who died of hemorrhage 3.5 months after the completion of CIRT, no moderate or severe late toxicities were observed.Conclusions: With few observed acute and late toxicities, salvage CIRT can provide effective short-term tumor control. Further research, preferably in a prospective fashion, will be required to confirm the efficacy and safety of salvage CIRT in this patient population.

Soft tissue sarcoma: how can posttreatment alterations be distinguished from recurrences?

The recognition of recurrent soft tissue sarcomas and the differentiation from post-treatment alterations is complex. This article aims to assist the clinical radiologist in the systematic evaluation of local follow-up imaging in soft tissue sarcoma patients. Soft tissue sarcomas encompass multiple entities with different recurrence rates and follow-up intervals. Approved and up to date recommendations are provided, including imaging techniques. The past medical history of the patient, the clinical situation and previous therapies should be known in detail, including surgery, radiation therapy and chemotherapy. Previous imaging results should be consulted, if available. This article describes the time-dependent imaging spectrum of local post-therapeutic as well as local treatment-related complications. These include early complications, such as seromas, hematomas and infections, as well as late complications, including edema, fibrosis and joint stiffness, and also inflammatory pseudotumors, which may occur after variable time intervals. The imaging appearance of local recurrent and radiation-associated sarcoma are elucidated. In particular, magnetic resonance imaging (MRI) criteria are provided, which may help in differentiating post-therapeutic alterations from recurrent soft tissue sarcomas.

Stereotactic Body Radiotherapy (SBRT) for Metastatic and Recurrent Soft Tissue and Bone Sarcomas

Stereotactic Body Radiotherapy (SBRT) for Metastatic and Recurrent Soft Tissue and Bone Sarcomas

Radiotherapy and hyperthermia with curative intent in recurrent high risk soft tissue sarcomas

Purpose: Radiotherapy before or after resection is one of the pillars of treatment for localised high risk soft tissue sarcomas. Treatment intensification has been described with concurrent chemotherapy and hyperthermia. The aim of this study is to assess local control after multimodal treatment, focussing on the treatment of local recurrences after surgery only.Patients and methods: Of 42 patients treated in a prospective protocol with radiotherapy and hyperthermia, nine were treated for isolated local recurrences without metastatic spread. Most patients were treated with trimodal therapy including chemotherapy with ifosfamide and underwent resection whenever possible. Median follow-up was 1.4 years.Results: The treatment was well tolerated. Estimated disease free survival, distant metastases free survival and local control for the whole cohort after 1.5 years were 66, 73 and 88%, respectively. Neoadjuvant vs. adjuvant treatment influenced local control with a trend to statistical significance. Resection status did not influence local control. The cohort of patients treated for local recurrence after surgery alone had a significantly impaired local control compared to multimodal treatment at primary diagnosis (100 vs. 52%, p < 0.001).Conclusions: With multimodal therapy including radiotherapy and hyperthermia local tumour control is achievable even in locally recurrent tumours. The clear-cut difference of the treatment of local recurrence in contrast to primary diagnosis might either reflect difficulties in diagnosis and treatment of local recurrences or biological aggressiveness of recurrent tumours. However, we recommend to consider multimodal treatment at primary diagnosis of high risk soft tissue sarcomas.

Pulmonary tumor embolism secondary to soft tissue and bone sarcomas: a case report and literature review

BackgroundTumor embolisms (TE) are an underappreciated source of pulmonary embolisms in sarcoma. Most evidence in the literature is limited to case reports and none have described the presence of TE secondary to myxofibrosarcoma. We report the first case of myxofibrosarcoma TE and perform a review of the literature for TE secondary to bone and soft tissue sarcomas (STS).Case presentationA 36-year-old female presented with debilitating pain of the right upper extremity secondary to a recurrent soft tissue sarcoma. She had distant metastasis to the lung. An MRI revealed a 25-cm shoulder mass involving the proximal arm muscles with encasement of the axillary artery, vein, and brachial plexus. A palliative forequarter amputation was performed and tumor thrombus was evident within the axillary artery and vein. Postoperatively, she developed an acute onset of dyspnea and hypoxia. A computed tomography scan revealed a pulmonary saddle embolism. A bilateral lower extremity venous duplex was negative. She became hemodynamically unstable despite resuscitation and was placed on vasopressor support. A transthoracic echocardiogram revealed elevated pulmonary artery pressure, tricuspid regurgitation, right heart dilation, and reduced right heart systolic function consistent with acute cor pulmonale. The patient did not want to pursue a median sternotomy with pulmonary artery embolectomy and expired from cardiopulmonary arrest within 24 h of the operation. The final pathology revealed a 25 × 16 × 13 cm high-grade myxofibrosarcoma with invasion into the bone, skin, and neurovascular bundle as well as evidence of tumor thrombus.ConclusionTE is a rare but deadly cause of pulmonary embolism in sarcoma. A high index of suspicion is necessary in individuals who present with respiratory-related symptoms, especially dyspnea. Diagnostic confirmation with a computed tomography scan of the chest and echocardiogram should be rapid. Unlike venous thromboembolism, pulmonary embolectomy remains the preferred therapeutic approach.

Generation and characterization of ErbB2-CAR-engineered cytokine-induced killer cells for the treatment of high-risk soft tissue sarcoma in children.

Pediatric patients with recurrent, refractory or advanced soft tissue sarcoma (STS) who are simultaneously showing signs of cumulative treatment toxicity are in need of novel therapies. In this preclinical analysis, we identified ErbB2 as a targetable antigen on STS cells and used cytokine-induced killer (CIK) cells transduced with the lentiviral 2nd-generation chimeric antigen receptor (CAR) vector pS-5.28.z-IEW to target ErbB2-positive tumors. Solely CIK cell subsets with the CD3+ T cell phenotype showed up to 85% cell surface expression of the respective CAR. A comparison of wildtype (WT), mock-vector and ErbB2-CAR-CIK cells showed, that engineered cells exhibited diminished in vitro expansion, retained WT CIK cell phenotype with higher percentages of differentiated effector memory/effector cells. Activating natural killer (NK) cell receptor NKG2D-restricted target cell recognition and killing of WT and ErbB2-CAR-CIK cells was maintained against ErbB2-negative tumors, while ErbB2-CAR-CIK cells demonstrated significantly increased cytotoxicity against ErbB2-positive targets, including primary tumors. ErbB2-CAR- but not WT CIK cells proliferated, infiltrated and efficiently lysed tumor cell monolayers as well as 3D tumor spheroids.Here, we demonstrate a potential cell therapeutic approach using ErbB2-CAR-CIK cells for the recognition and elimination of tumor cells expressing ErbB2, which we identified as a targetable antigen on high-risk STS cells.

A prospective study of proton reirradiation for recurrent and secondary soft tissue sarcoma

Background and purposeProton reirradiation for sarcoma has not been previously described. We hypothesized that this strategy would provide favorable toxicity and survival outcomes. Material and methodsPatients with soft tissue sarcoma in a previously-irradiated field were enrolled on a prospective trial of proton reirradiation. The primary endpoint was provider-reported acute toxicity. Secondary endpoints included late toxicities, local control, and overall survival. Results23 patients underwent proton reirradiation. Median time between radiation courses was 40.7months (range 10–272). No grade 4–5 toxicities were observed. One patient (4%) experienced acute grade 3 dysphagia. Common grade 2 acute toxicities were fatigue (26%), anorexia (17%), and urinary incontinence (13%). There were two grade 3 late wound infections (10%) and one grade 3 late wound complication (5%). Grade 2 late complications included lymphedema (10%), fracture (5%), and fibrosis (5%). At a median follow-up of 36months, the 3-year cumulative incidence of local failure was 41% (95% CI [20–63%]). Median overall survival and progression-free survival were 44 and 29months, respectively. In extremity patients, amputation was spared in 7/10 (70%). ConclusionsProton reirradiation of recurrent/secondary soft tissue sarcomas is well tolerated. While longer follow-up is needed, early survival outcomes in this high-risk population are encouraging.

Comparative analysis of cell cycle parameters in primary and recurrent soft tissue sarcomas.

e22538 Background: The purpose of the study was to determine DNA content and distribution of cells in cell cycle phases by flow cytometry in patients with primary and recurrent soft tissue sarcomas. Methods: 60 patients with soft tissue sarcomas (STS) were recruited: 30 with primary tumors and 30 with recurrent ones. Mean age of patients with primary STS was 56±5.4 years, with recurrent STS – 55±6.7 years. DNA content was determined using the BD Facs Cantoo II flow cytometer with CycleTEST PLUS DNA Reagent Kit (Becton Dickinson). The data were processed using ModFit LT program. Results: Comparative analysis of the cell cycle kinetics showed an increase in the percentage of cells in G2+M phase by 2 times in diploid and by 2.1 times in aneuploid recurrent tumors in comparison with primary ones (1.8±0.5% vs. 0.9±0.1% for diploid tumors; 5.4±2.2% vs. 2.6±0.7% for aneuploid tumors). An increase in the percentage of aneuploid tumors was found in recurrent G2 and G3 tumors (from 50% in primary to 66.7% in recurrent G2 tumors and from 63.25% in primary to 85% in recurrent G3 tumors). Mean content of aneuploid cells in recurrent G2 tumors was 2.2 times higher (p≤0.05), while the differences in primary and recurrent G3 tumors were not significant. The percentage of aneuploid tumors depended on the disease stage and increased in stages IIb and III in recurrent tumors, compared to primary ones (from 37.5% to 71.4% in recurrent st. IIb; and from 65% in primary st. III to 72.7% in recurrences) (p≤0.05). Conclusions: DNA analysis by flow cytometry demonstrated a high biologic potential of both primary and recurrent tumors. Some values in the mitotic cycle in recurrent tumors were probably associated with adjuvant therapy, as well as influenced by the coefficient of two parameters – the percentage of cells in G2+M phase and the cell loss factor determining a high malignant potential of these tumors.

Immune response, safety, and survival impact from CMB305 in NY-ESO-1+ recurrent soft tissue sarcomas (STS).

11006 Background: CMB305 is an active immunotherapy regimen designed to generate and expand anti-NY-ESO-1 T cells. It consists of LV305, a dendritic cell targeting lentiviral vector encoding NY-ESO-1, and a boost with G305, an NY-ESO-1 recombinant protein plus GLA-SE, a TLR-4 agonist. An LV305 phase 1 study demonstrated a 1-yr survival of 81% and induction of anti-NY-ESO-1 T cells in sarcoma patients (pts). This first-in-human study of CMB305 examined safety, immunogenicity, and efficacy in pts with NY-ESO-1 positive (+) solid tumors. Methods: Adults with previously treated NY-ESO-1+ sarcomas, NSCLC, ovarian cancer were enrolled in a 3+3 dose-escalation with an expansion phase 1 study. The CMB305 regimen included 4 intradermal injections of LV305 at 109 or 1010 vector genomes, alternating with 3 intramuscular G305 injections at 250 µg for 3 months, then bimonthly G305 injections up to 1 yr. Results: As of 31Dec2016, 25 pts with STS (15 synovial (SS), 8 myxoid/round cell liposarcoma (MRCL), 2 other) were evaluable for safety; 23 SS/MRCL pts were evaluable for immune response (IR) and efficacy. All SS and MRCL pts received prior therapy for locally advanced/metastatic disease, 67% &gt; = 2 prior chemo regimens. No DLTs were observed; treatment related AEs were grade 1 and 2, except 1 pt with grade 3 SAE (prostatic pain). Of 11 SS/MRCL pts tested, 64% pts developed NY-ESO-1 specific T cells and 72% pts anti-NY-ESO-1 antibodies. T cell receptor sequencing indicated increased clonality, and antigen spreading after CMB305. Best response by immune related response criteria was stable disease in 8/15 (53%) SS pts and 6/8 (75%) MRCL pts. The 3 month PFS rate was 74% and 75% for SS and MRCL pts. Median survival has not been reached with 1-yr survival rate of 86% and 100% for SS and MRCL pts. Conclusions: CMB305 is safe, well tolerated, and demonstrates a survival rate that is favorable when compared with approved agents for recurrent STS. CMB305 resulted in a stronger and broader integrated IR than LV305, including antigen spreading. These data warrant further investigation of CMB305 as a monotherapy in a randomized clinical study in STS. A randomized study of CMB305 in combination with atezolizumab in SS/MRCL pts is ongoing. Clinical trial information: NCT02387125.

Response of advanced soft tissue sarcoma to apatinib: A retrospective analysis.

e22502 Background: Soft tissue sarcomas (STSs) are rare but malignant tumors with high risks of local recurrence and distant metastasis. Promising efficacy of apatinib was reported in several subtypes of STSs (Dong et al. 2016, Medicine 95: e4368; Ji et al. 2016, OncoTargets and therapy 9:643-647). We aimed to preliminarily assess the short efficacy and safety of apatinib, an oral tyrosine kinase inhibitor targeting VEFGR-2, in patients with advanced STS. Methods: The medical records of 31 patients who received apatinib between September 2015 and August 2016 were retrospectively reviewed to evaluate the short efficacy, time to progression (TTP) and safety. Results: Nineteen (61.3%) patients taken apatinib after failing second or even more lines of cytotoxic chemotherapy, 8 (25.8%) patients received apatinib as second-line therapy, and 4 (12.9%) cases who refused chemotherapy was given apatinib as first-line therapy. In the study cohort, one patient was treated with apatinib as adjunctive therapy after ablation, while the remaining 30 as salvage therapy. Administration was stopped in 6 cases due to adverse events (n = 3) or personal reasons (n = 3). As a result, 24 patients were eligible for tumor response to apatinib evaluation, and 25 patients were available for survival analysis. The objective response rate was 33.3% and clinical benefit rate was as high as 75.0%. The median TTP was 4.3 months (range, 1.8–11.6 months). Most of the AEs were at grade 1 or 2. The grade 3 AEs were hypertension (n = 2, 6.5%), hand-foot syndrome (n = 2, 6.5%), and diarrhea (n = 1, 3.2%). No grade 4 AE or drug-related mortality occurred. Conclusions: Apatinib showed promising efficacy and acceptable safety profile in metastatic or recurrent STS, giving rationale clinical evidence to conduct clinical trials.

Efficacy and safety of gemcitabine plus docetaxel in Japanese patients with unresectable or recurrent bone and soft tissue sarcoma: Results from a single-institutional analysis.

BackgroundCombination therapy with gemcitabine and docetaxel has been reported to be a good therapeutic strategy for patients with soft tissue sarcoma. The aim of the present study was to analyze the efficacy and toxicity of gemcitabine with docetaxel in Japanese patients with advanced bone and soft tissue sarcoma.Patients and methodsWe retrospectively analyzed the effect of gemcitabine and docetaxel therapy on overall response, progression-free survival, overall survival, and toxicity in 42 patients with bone or soft tissue sarcoma who had received the therapy between October 2006 and September 2015, at Tohoku University Hospital.ResultsThe median age was 55 years; 23 patients were men, and 19 were women. Eight had bone sarcoma and 34 had soft tissue sarcoma. Forty patients (95%) had previously been treated with one or more chemotherapeutic regimens. The overall response rate was 6.9% and the disease control rate was 55%. The median progression-free survival was 2.3 months and the median overall survival was 14.3 months. Grade 3 or more neutropenia and febrile neutropenia were observed in 74% and 4.8% of all patients, respectively.ConclusionThe response rate was lower and myelosuppression was more frequently observed than in other previous reports. On the other hand, most of toxicities were enough manageable. In addition, some patients had long survival with a good response. Our study supports the notion that gemcitabine and docetaxel therapy is a good therapeutic option for treating patients with advanced soft tissue sarcoma as well as bone sarcoma, also in Asian populations.

Focal nodular hyperplasia that mimicked a liver metastasis from a soft tissue sarcoma: a case report

BackgroundImaging modalities (computed tomography (CT), ultrasonography, and magnetic resonance imaging (MRI)) have only limited ability to distinguish liver focal nodular hyperplasia (FNH) from metastatic liver tumors. Here, we report a patient who underwent surgery for benign FNH that mimicked a liver metastasis from soft tissue sarcoma (STS).Case presentationA 23-year-old man with a history of several surgeries for metastatic abdominal STS, developed a hepatic tumor accompanying peritoneal STS recurrence. He was diagnosed with a metastatic liver tumor from the STS, based on imaging studies for the hepatic tumor that showed a growing hypervascular lesion and hypo-intensity in hepatic phase on dynamic CT and MRI. However, when the liver and peritoneal tumors were resected, histological diagnosis showed the hepatic tumor to be benign liver FNH.ConclusionsAlthough FNH should be considered as a differential diagnosis for hypervascular hepatic tumors, it has few typical findings, and its appropriate management is controversial. A lesion strongly suspected of being a metastatic liver tumor might require surgical resection.