Clinical Sarcoma Research最新文献

Background: Solitary fibrous tumour (SFT) is a rare soft tissue sarcoma with a low metastatic potential. A higher metastatic rate is observed in the high-grade/dedifferentiated variant. The most common expected site of distant spread are the lungs and the liver. Bone involvement is generally viewed as a late stage of disease spread. We report on a retrospective series of SFT patients relapsing with a single distant bone recurrence as first metastatic event, without evidence of other organ involvement.

Case presentation: All patients affected by a single distant bone metastasis from SFT as first distant event, without any evidence of other site of metastasis, observed at our Institution, were considered. Bone involvement from SFT was pathologically assessed in all cases and confirmed by expert pathologists. A total of six patients were retrospectively identified. Primary tumour arose from the meninges in four patients, from soft tissues in two. Bone metastases were located to the vertebrae, the hip, the acetabulum and the rib. In all cases, bone relapse was the first event, with one patient presenting a local relapse. Median time from the primary tumour and the evidence of bone relapse was 40 months (range 0-58). In 2/6 patients bone metastasis was treated with radiotherapy (RT), in 2/6 with surgery, in 2/6 with surgery plus RT. At a median follow-up of 55 months (range 23-88), 5/6 patients are alive (2/5 without disease, 3/5 with multicentric metastatic disease) and one is dead of disease. 2/6 patients did not relapse after the treatment of the bone metastasis.

Conclusions: This small series in a relatively rare histology suggests that isolated, possibly late, bone metastases are a plausible scenario, in particular in meningeal SFT. Notably, new bone lesions in a patient with a history of SFT should be always investigated. Exclusive local treatments may be an option, though collection of such series would be needed to define the best treatment strategy.

Background: Sclerotic tumours of the calvarial bones are rare and may be due to primary and secondary bone tumours as well as extradural tumours of meningeal origin.

Case presentation: We report a case of primary intraosseous meningioma (PIM) which arose in the frontal bone of a 63 year old woman who complained of progressive pain and thickening of the right skull. Radiology showed a large osteosclerotic lesion in the right frontal bone. Histology showed an intraosseous lesion containing dense fibrous tissue in which there were scattered cells that expressed epithelial membrane antigen and progesterone receptor. The tumour was partially resected and 3 years after operation has not recurred.

Conclusions: PIM is a rare tumour which needs to be distinguished from primary/secondary osteosclerotic calvarial bone tumours.

Background: A chronic inflammatory cell infiltrate is commonly seen in response to primary malignant tumours of bone. This is known to contain tumour-associated macrophages (TAMs) and lymphocytes; dendritic cells (DCs) and mast cells (MCs) have also been identified but whether these and other inflammatory cells are seen commonly in specific types of bone sarcoma is uncertain.

Methods: In this study we determined the nature of the inflammatory cell infiltrate in 56 primary bone sarcomas. Immunohistochemistry using monoclonal antibodies was employed to assess semiquantitatively CD45+ leukocyte infiltration and the extent of the DC, MC, TAM and T and B lymphocyte infiltrate.

Results: The extent of the inflammatory infiltrate in individual sarcomas was very variable. A moderate or heavy leukocyte infiltrate was more commonly seen in conventional high-grade osteosarcoma, undifferentiated pleomorphic sarcoma and giant cell tumour of bone (GCTB) than in Ewing sarcoma, chordoma and chondrosarcoma. CD14+/CD68+ TAMs and CD3+ T lymphocytes were the major components of the inflammatory cell response but (DC-SIGN/CD11c+) DCs were also commonly noted when there was a significant TAM and T lymphocyte infiltrate. MCs were identified mainly at the periphery of sarcomas, including the osteolytic tumour-bone interface.

Discussion: Our findings indicate that, although variable, some malignant bone tumours (e.g. osteosarcoma, GCTB) are more commonly associated with a pronounced inflammatory cell infiltrate than others (e.g. chondrosarcoma. Ewing sarcoma); the infiltrate is composed mainly of TAMs but includes a significant DC, T lymphocyte and MC infiltrate.

Conclusion: Tumours that contain a heavy inflammatory cell response, which includes DCs, TAMs and T lymphocytes, may be more amenable to immunomodulatory therapy. MCs are present mainly at the tumour edge and are likely to contribute to osteolysis and tumour invasion.

Background: Advances in treatment of sarcoma patients has prolonged survival but has led to increased disease- or treatment-related complications resulting in greater number of admissions to the intensive care unit (ICU). Survival and long-term outcome information about such critically ill patients with sarcoma is unknown.

Methods: The primary objective of the study was to determine the ICU and post-ICU survival rates of critically ill sarcoma patients. Secondary objectives included determining the modifiable and non-modifiable predictors of poor survival. We performed a retrospective chart review of sarcoma patients admitted to the ICU at The University of Texas MD Anderson Cancer Center between January 1, 2005, and December 31, 2012. Main outcome measures were ICU mortality, in-hospital mortality and 1, 2, and 6-month survival rates. Covariates such as histological diagnosis, disease characteristics, chemotherapy use, Charlson comorbidity index, Sequential Organ Failure Assessment (SOFA) scores, and clinical findings leading to ICU admission were analyzed for their effects on survival.

Results: We identified 172 admissions over the 8-year study period hat met our inclusion criteria. The study population was 45.9 % males with a median age of 52 years. The most common sarcoma subgroups were high-grade unclassified sarcoma (25 %) and bone tumors (17.4 %). The ICU mortality rate was 23.3 % (95 % confidence interval [CI], 16.9-29.6 %), and an additional 6.4 % of patients died before hospital discharge (95 % CI, 22.9-37.1 %). 6-month OS rates were 41 %. The median SOFA scores on admission were 6 (inter quartile range (IQR), 3.5-9) in ICU survivors and 10 (IQR, 6.5-14) in ICU non-survivors. Increase in SOFA scores ≥6 led to poor outcomes (ICU survival 13.3 %, OS 6.7 %). Charlson comorbidity index (HR 1.139, 95 % CI 1.023-1.268, p = 0.02) and discharge SOFA scores (HR 1.210, 95 % CI 1.141-1.283, p < 0.0001) correlated with overall survival.

Conclusions: Our results suggest that patients that are admitted to the ICU for respiratory failure, cardiac arrest, septic shock, acute renal failure or acidosis and also have a high SOFA score with subsequent worsening in the ICU have poor prognosis. Based on the retrospective data which needs further validation we can recommend that judicious approach should be taken in patients with predictors of poor survival before subjecting them to aggressive treatment.

Background: There is a paucity of data on the current management of patients with advanced soft tissue sarcoma (STS) in the Australian health care setting. This study utilised the Australian sarcoma database to evaluate the patterns of care delivered to patients with advanced STS at Australian sarcoma services.

Methods: Prospectively collected data from six sarcoma centres in Australia were sourced to identify patients diagnosed with advanced STS between 1 January 2010 and 31 December 2012. Descriptive statistics were analysed for patient demographics, clinicopathological characteristics and treatment patterns. Overall survival was estimated using the Kaplan-Meier product limit method.

Results: Of 253 patients with advanced STS, four major STS subtypes were identified: undifferentiated pleomorphic sarcoma (23 %), leiomyosarcoma (17 %), liposarcoma (14 %), and synovial sarcoma (8 %); with the rest grouped as "other STS" (38 %). Approximately one-third of patients received palliative systemic therapy with the most common first-line therapy being doxorubicin alone (50 %). A small percentage of patients participated in clinical trials (20 %). Palliative radiotherapy was utilised mostly for treatment of symptomatic distant metastases and one-third of patients underwent metastasectomy, most commonly for pulmonary metastases. The median overall survival (OS) in this series was 18 months and no significant difference in OS was observed across different STS histological subtypes.

Conclusions: This is the first detailed study outlining patterns of care for Australian patients with advanced STS managed at sarcoma services. These data highlight a particular area of weakness in the lack of clinical trials for sarcoma patients and also serve as an important reference point for understanding how practice may change over time as treatment options evolve.

Background: Most GISTs have mutations in KIT or PDGFRA. Patients with advanced GIST with KIT exon 9, PDGFRA mutation or WT for KIT and PDGFRA have a worse progression-free survival (PFS) compared to patients with KIT exon 11 mutated tumors. We evaluated the immunohistochemical (IHC) expression of p-IGF1R (Y1316) and MMP3 as predictors of PFS or overall survival (OS).

Methods: Ninety-two advanced GIST patients included in GEIS-16 study with KIT and PDGFRA mutational information were examined for p-IGF1R (Y1316) and MMP3 expression in a tissue micro-array. To study activation of the IGF1R system, we have used an antibody (anti-pY1316) that specifically recognizes the active phosphorylated form of the IGF1R. DNA was extracted from paraffin-embedded tissues and intronic PCR primers were used to amplify exons 9, 11, 13 and 17 of KIT, 12 and 18 of PDGFRA. Bidirectional sequencing with specific primers was performed on a ABI3100 sequencer using the Big Dye Terminator v3.1 kit. Multivariate model was built using a stepwise automated variable selection approach with criterion to enter the variable in the model of p < 0.10 and criterion to keep the variable in the model of p < 0.05. PFS was computed as the date of imatinib initiation to progression or death. Overall survival was defined as the time from imatinib initiation to death.

Results: Phospho-IGF1R was expressed only in 9 % (2/22) of cases without KIT mutation. MMP3 expression was detected in 2/5 patients (40 %) with PDGFRA mutation, 1/16 patients (6 %) with WT genotype and 7/71 patients (10 %) of KIT mutant patients. At univariate analysis KIT exon 11/13 mutation had better PFS than patients with exon 9 mutation, PDGFRA mutation or WT genotype (p = 0.021; HR: 0.46; 95 %CI (0.28-0.76). Less than 24 months disease free-interval (HR 24.2, 95 % CI 10.5-55.8), poor performance status (PS) (HR 6.3, 95 % CI 2.5-15.9), extension of disease; >1 organ (HR 1.89; 95 % CI 1.03-3.4) and genotype analysis (HR 0.57, 95 % CI 0.37-0.97) but not immunophenotype analysis (HR 1.53; 95 % CI 0.76-3.06) were the strongest prognostic factors for PFS in the multivariate analysis.

Conclusions: Our results do not support p-IGF-1R and MMP3 evaluation in non-selected GIST patients but evaluation of this immunophenotype in WT and mutant PDGFR mutation in larger group of GIST patients, deserve merits.

Sarcomas are a heterogeneous group of mesenchymal malignancies. In recent years, studies have demonstrated that inhibition of angiogenic pathways or disruption of established vasculature can attenuate the growth of sarcomas. However, when used as monotherapy in the clinical setting, these targeted antiangiogenic agents have only provided modest survival benefits in some sarcoma subtypes, and have not been efficacious in others. Preclinical and early clinical data suggest that the addition of conventional chemotherapy to antiangiogenic agents may lead to more effective therapies for patients with these tumors. In the current review, the authors summarize the available evidence and possible mechanisms supporting this approach.

Background: Angiosarcoma is a rare subgroup of soft tissue sarcomas associated with poor prognosis, but paclitaxel has been shown to be active in pretreated metastatic disease. We investigated the efficacy and safety of weekly paclitaxel as first-line chemotherapy in adult patients with metastatic angiosarcoma.

Methods: A retrospective study using the Samsung Medical Center (Seoul, Korea) cancer chemotherapy registry was performed on 21 consecutive patients with angiosarcoma who were treated with weekly paclitaxel as first-line therapy for metastatic disease between Oct. 2008 and Dec. 2014. We excluded patients who were enrolled in clinical trials to ensure the results would reflect the real-world outcomes obtained in a daily clinical setting. Endpoints included efficacy in terms of response rate, progression-free survival (PFS), overall survival (OS) and safety.

Results: Among 21 patients, 15 (71 %) were male and the median age was 53 years (range, 24-76). Primary sites of angiosarcoma were the visceral organs (33 %), scalp (29 %) and heart (23 %). The median number of metastatic sites was two (range, 1-5) with the lungs being the most frequently involved site. Weekly paclitaxel was generally well tolerated: the major hematologic toxicity was grade 1/2 anemia (24 %). Among non-hematologic toxicities, grade 1/2 peripheral neuropathy was most commonly observed (67 %). Objective response was observed in 11 (52 %) patients (4 complete and 7 partial responses). With a median follow-up of 21 months, the estimated median PFS and OS were 5.7 months (95 % CI 5.1-6.3) and 18.6 months (95 % CI 9.9-27.3), respectively.

Conclusions: In this retrospective study, first-line chemotherapy with weekly paclitaxel demonstrated clinically relevant efficacy and tolerability in unselected Korean patients with metastatic angiosarcoma. It is encouraging that response rate and PFS for Korean patients were similar to those reported in Western reports.