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Bone and Soft Tissue Sarcomas represent approximately 1% of all malignant tumours. Delays in diagnosis are frequent and the average size of Sarcomas at diagnosis has averaged 10cm for many years. In 1999 guidance was produced by NICE with the aim of leading to the earlier diagnosis of common cancers – including Sarcomas. We have attempted to analyze whether this guidance has had any impact on either the size of the tumours at diagnosis or the symptom duration prior to diagnosis experienced by the patients.
Data for patients referred to the Royal Orthopaedic Hospital in Birmingham between 1992 and 2007 with Bone Sarcomas (n=1592) and Soft Tissue Sarcomas (n=2004) were analysed to determine the effect of the guidance. For Bone Sarcomas the mean size of the tumours decreased from 11.2cm prior to the guidance to 10.7cm after the guidance but the change was not statistically significant (p=0.09). The mean duration of symptoms increased from 18 to 21.2 weeks (p=0.01). For Soft Tissue Sarcomas, mean size fell from 10.8cm to 9.5cm (p<0.001), however the duration of symptoms actually increased from 27.3 to 32.1 weeks (p=0.01). Statistical modelling using restricted cubic splines confirmed these trends in the data.
These results show that whilst there may have been a slight improvement in the size at diagnosis of Soft Tissue Sarcomas, overall most patients still experience a long delay between the onset of symptoms and diagnosis and commencement of treatment. It is difficult to conclude that the early diagnosis guidance produced in 1999 has had a significant effect on the basis of this study. Strategies to improve awareness of the symptoms and clinical features of Bone and Soft Tissue Sarcomas are still urgently required.
Early diagnosis is assumed to improve patient survival, but whether symptom interval (SI i.e. the period between the onset of the first symptoms signs of the disease and its definitive diagnosis) has significant impact on outcome or not remain unclear.
Methods
In a series of 575 patients < 21 years of age with soft tissue sarcomas (STS) we investigated the association patterns between SI patient/tumour characteristics or disease outcome. The analysis was based on multivariate models (linear for association's patient/tumour characteristics and Cox's for survival).
Results
The SI ranged between one week and 60 months (median 2 months) and tended to be longer the older the patient (i.e. the interval was longer in adolescents than in children) and the larger tumour's size and for tumours located at the extremities and for “non rhabmomio sarcoma” STS (as opposed to rhabmomio sarcomas). A longer SI unfavourably influenced survival (p=0.002): for SI of 1, 12 and 24 months, the 5-year survival for rhabmomio sarcoma was 65%, 46% and 19% respectively. A different pattern of association between SI and survival emerged for different types of STS histology.
Retroperitoneal sarcomas (RS) are rare tumours that may reach considerable size at diagnosis and should optimally be treated by a specialized multidisciplinary team. In Sweden, we have since 10 years enforced referral of RS to sarcoma centers, but have experienced a considerable delay, which provides the basis for this study on delays in RS diagnosis and treatment.
We identified 33 patients treated for RS at the Southern Sweden Sarcoma Center (covering a population of 1.5 million), Lund University Hospital between 2003-2009. Data, including onset of symptoms, time to diagnosis and time to treatment were recorded from clinical files. Patient's delay was defined as the time from onset of symptoms to the first visit to a doctor, which could be a general practitioner or a specialist. Doctor's delay was defined as the time from the first visit to a doctor to the start of treatment, which was in most cases surgery.
In total, 30 patients were referred to the sarcoma centre for treatment. Complete data are available from 25 patients (13 men) with a median age of 62 (20-86) years. Median patient's delay was 15 days (0-9 months) and median doctor's delay was 97 days (0-40 months). Median doctor's delay was indeed somewhat longer (52 days) at the sarcoma centre than at the local hospitals (38 days). Some of the longest delays were caused by primary erroneous diagnosis (16 and 40 months) and comorbidity (4, 8 and 19 months) that required other medical procedures before surgery.
Though almost all patients with RS in Southern Sweden are referred to a sarcoma centre for treatment, delays are considerable for many patients with doctor's delays outnumbering patient's delays. Our findings demonstrate that centralisation per se is not sufficient to treat RS, but that optimized diagnostics and clinical management is needed also at sarcoma centers.
Aim
Grade is the most important predictor of the biological behaviour of soft tissue sarcomas. Assigning a pathologic grade is always a difficult task as discordance rate is 30-40% even among experienced sarcoma pathologists. Many of these tumours are heterogeneously large and only small fractions are sampled for biopsy. This emphasizes the need for an objective and accurate assessment of histology. Our aim is to evaluate the role of Choline as a tumour marker in (i) differentiating benign from malignant soft tissue tumour, (ii) to distinguish recurrent/residual tumours using in-vivo MR spectroscopy.
Methods
PMRS Study was performed at 1.5Tesla MRI machine of the lesions in 25 patients. Single-voxel (SVS) study has been done in 10 cases and chemical shift imaging (CSI) study characterised the heterogeneity of the tumour in 15 cases by using point – resolved spectroscopic sequence (PRESS) with echo time TR=2000/TE = 30, 135 & 270 msec. The choline peak, identified at 3.2 ppm in spectra was considered significant. MRS results and histopathologic findings were correlated and P < 0.001, considered being significant.
Aim
Grade is the most important predictor of the biological behaviour of soft tissue sarcomas. Assigning a pathologic grade is always a difficult task as discordance rate is 30-40% even among experienced sarcoma pathologists. Many of these tumours are heterogeneously large and only small fractions are sampled for biopsy. This emphasizes the need for an objective and accurate assessment of histology. Our aim is to evaluate the role of Choline as a tumour marker in (i) differentiating benign from malignant soft tissue tumour, (ii) to distinguish recurrent/residual tumours using in-vivo MR spectroscopy.
Methods
PMRS Study was performed at 1.5Tesla MRI machine of the lesions in 25 patients. Single-voxel (SVS) study has been done in 10 cases and chemical shift imaging (CSI) study characterised the heterogeneity of the tumour in 15 cases by using point – resolved spectroscopic sequence (PRESS) with echo time TR=2000/TE = 30, 135 & 270 msec. The choline peak, identified at 3.2 ppm in spectra was considered significant. MRS results and histopathologic findings were correlated and P < 0.001, considered being significant.
Since1986 we have monitored the actual diagnosis of all cases referred to our Unit with the diagnosis of ‘possible primary malignant bone tumour’. We have excluded all patients referred with a known diagnosis of either a benign condition or known to have bone metastases. In most cases the suspected diagnosis was based on X-rays alone, sometimes supported by further imaging.
Method
Retrospective review of a prospective database that was started in 1986 identifying the actual diagnosis.
Results
There were 5922 patients with a confirmed diagnosis over the 23 year time period of this study. 2205 (37%) were found to have a primary malignant bone sarcoma and 1309 (22%) had a benign bone tumour. 992 patients had a general orthopaedic condition (e.g. geode or a vascular necrosis) whilst 303 (5%) had a haematological malignancy and 289 (4.9%) infection. 533 patients (9%) had metastases. There was a similar pattern of frequency of all diagnoses except for metastatic disease and haematologic malignancy at different ages. The incidence of metastases increased from the age of 35 onwards
Aim
To determine whether delayed diagnosis (lapse from initial symptoms to the beginning of treatment) has influence on the possibilities of crossing the physis by the tumour, and/or on the outcome in pediatric patients with high grade metaphyseal osteosarcoma.
Patients and methods
The clinical records, image methods and the histology reports of 157 metaphyseal paediatric osteosarcomas were reviewed. The mean follow-up time was 102 months. Location, histological subtype, time from initial symptoms to start of treatment, major diameter, % of necrosis, physis crossed by the tumour or not, and outcome (recurrence, metastases and status) were recorded in a SPSS v15.0 file.
Aim
Multiple (hereditary) osteochondroma (MO) is a rare autosomal dominant disease. Previous reports show that the risk of a malignant degeneration varies between 5-25%, but these are often combined with data on other cartilaginous diseases. The aim of this study was to establish clinical and radiological parameters that could identify a group of MO patients who are at risk for peripheral chondrosarcoma.
Methods
A database of 64 MO patients surgically treated between 1980-2009 was established. For 24 patients full radiological (including MRI), surgical and pathological records were complete. This group contained 14 osteochondroma patients and 10 chondrosarcoma patients. Non-parametric tests and Kaplan-Meier survival analysis were used to establish a cartilage-cap thickness cut off point and a volume cut off point.
Aim
Improving the quality of clinical and radiologic differential diagnosis of intramedullary tumours of long bones.
Methods
A database includes clinical and radiologic (X-ray, CT and MRI methods) signs of 106 patients with osteosarcoma (n = 44), chondrosarcoma (n = 31) and giant cell tumour (n = 31). Multivariate analysis of clinical and radiologic characteristics and developing informative set of criteria (decision rule) for the differential diagnosis of osteosarcoma, chondrosarcoma and giant cell tumour were provided with program «ASTA».
Background
Angiosarcoma is a rare complication of breast cancer treatment. In order to define predictors, clinical presentation, and outcome, we characterized a population-based 50-year cohort of angiosarcomas after breast cancer.
Methods
Clinical data were collected from all females with previous breast cancer who developed angiosarcomas/lymphangiosarcomas on the thoracic wall/upper extremity between 1958 and 2008 in the Southern Swedish health care region.
Aim
Bumps and lumps of the hand are a common cause for consultation in general practice. However not all of these lesions are of true neoplastic nature and malignant tumours are a rarity in this location.
Method
The records of all tumours of the hand and wrist treated surgically at our institution in the period 1994 to 2009 were reviewed. Because of their non-neoplastic nature typical lesions of the hand such as ganglion cysts or palmar fibromatosis and the like were not included in this study. Histological entity, location, radiographic and clinical findings were analysed; malignant tumours were followed up by X-ray and MRI.
Background
Bone lesions in Ewing's sarcoma (ES/PNET) have been traditionally diagnosed with bone Scan. PET-scan is emerging as a promising investigative modality for detection of metastatic lesions. In this prospective study, we compare the utility of both to detect the metastatic sites.
Methods
One hundred and seventy five histologically proven cases of ESPNET from 2004-2009 were prospectively staged with bone scan and PET-scan with Breath- hold CT scan- thorax. The diagnostic value of PET-scan to pick up metastatic lesions was compared with bone scan.
Aim
Accurate and reliable patient information plays a crucial role in the multidisciplinary treatment of malignancies helping to ensure compliance of the patients and their relatives with often long-lasting and stressful treatment. The English version of the online encyclopaedia Wikipedia has been recently reported to be the prominent source of online health information. However, there is little information concerning the quality of information found in Wikipedia.
Method
We therefore created a questionnaire concerning of 20 questions asking for scope, completeness and accuracy of information found on osteosarcoma. Three independent observers tested the English version of Wikipedia as well as the patient version and the health professional version of the website of the National Cancer Institute. Answers (scores 0-3) were verified with authoritative resources and international guidelines.
Aim
To present our experience and results of percutaneus sclerotherapy of aneurysmal bone cysts (ABC).
Method
All patients from January 2007 to September 2009, where radiology and cytology were consistent with ABC (n=20), were treated with repeated injections of 30 mg/ml polidocanol. The mean age was 16 (5-27) years. There were 13 lesions in the long bones, 2 in the pelvic bones, 2 in the sacrum, 2 in the foot, and 1 in a finger. The sclerotherapy was performed under fluoroscopic or CT guidance and under local or general anesthesia. Each injection consisted of 2 mg polidocanol per kg body weight. Three injections with an interval of 4 weeks were most commonly scheduled. Radiological assessment was performed regularly after the last injection. Injections were continued if the lesion had not healed.
CT guided percutaneous radiofrequency thermocoagulation is the treatment of choice for osteoid osteomas. Good results with a low complication rate have been shown for spinal lesions. When lesions are within close proximity to neurological structures or if patients have radicular symptoms surgery rather than radiofrequency ablation has been advocated. We present our experience of radiofrequency ablation of spinal osteoid osteomas which are less than 5mm from neurological structures, including those causing radicular symptoms.
Data was collected prospectively on all patients with a spinal osteoid osteoma within 5mm of nerve roots or the spinal cord as measured on CT scanning.
There were nine patients, five female and four male with a mean age of 15 years. Four tumours were located in the thoracic spine, three in the lumbar spine and two in the cervical spine. The mean distance to the nearest neurological structure was 3mm. Radicular symptoms were present in two patients. The mean number of probe positions used was two. Lesions were heated to 90 degrees for 5 minutes for each probe position. There were two cases of recurrence, both treated successfully with one further procedure each. There were no cases of neurological injury. The two patients with radicular symptoms had full resolution of their symptoms. At a mean follow up of 2 years following treatment all patients are asymptomatic.
Radiofrequency ablation can be safely performed to treat osteoid osteomas located within 5mm of neurological structures and has a low rate of recurrence.
Aim
To study the efficacy of Zoledronic acid in the treatment of benign osteolytic tumours or tumour like conditions of bone as a therapeutic or as an adjuvant agent
Method
31 patients- 19 female, 12 male, age from 8 yrs to 42 yrs, were treated with intravenous zoledronic acid. In 17 patients (fibrous dysplasia-10, nonossifying fibroma- 4, UBC- 3) zoledronic acid alone was used as a therapeutic agent. In 14 patients (ABC- 3, GCT- 11), it was used as an adjuvant agent after curettage. Four patients presented with pathological fracture. In all patients, 4 mg. zoledronic acid was given at 2 monthly intervals. In 12 adult patients, in addition oral bisphosphonates - alendronate was given weekly for at least 6 months.
Aim
Local recurrence after surgery of soft tissue sarcomas is dependent on surgical margins. Wide margins require large resections which may lead to impaired function or loss of limb. In some cases it may be technical impossible or even ethical unacceptable to achieve ideal surgical margins. Standard adjuvant treatment in such cases is ionising radiation, which may cause severe toxic side effects.
PCI is a unique procedure for site-specific delivery of several types of membrane impermeable molecules. The technology is based on the photochemical induced cytosolic release of endocytosed macromolecules from endosomes and lysosomes into the cytosol. PCI has in this study been evaluated as an adjuvant to the surgical resection of sarcoma.
Method
Human fibrosarcom (HT1080) was transplanted to athymic mice. The photosensitizer aluminium phthalocyanine disulfonat (AlPcS2a), and bleomycin (BLM) was systemically administrated 48 hours and 30 minutes respectively prior to surgery and light exposure. After resection with intralesional margin the tumour bed was illuminated at 670 nm (15 J/cm2).
Aim
The recent discovery of small non-coding RNAs, so-called micro RNAs (miRNAs), has provided new insights into cancer diagnosis. Several studies have shown that profiles of miRNA expression differ between normal tissue and tumour tissue and vary among tumour types. To exploit this difference, we evaluated the feasibility of using muscle-specific miRNAs (miR-1, 133a, 133b, 206) as biomarkers of rhabdomyosarcoma (RMS).
Method
Total RNA was extracted from 16 cell lines (7 RMS, 4 neuroblastoma, 3 Ewing sarcoma and 2 malignant rhabdoid tumour) and 21 tumour specimens (7 RMS, 1 Ewing sarcoma, 4 undifferentiated sarcoma, 1 osteosarcoma, 1 alveolar soft part sarcoma, 2 neuroblastoma, 2 Wilms tumour, 1 malignant rhabdoid tumour, 1 adrenal carcinoma and 1 retinoblastoma). miRNA was quantified by real-time RT-PCR. The expression levels of miRNAs were calculated utilizing the delta-delta Ct method, normalised to the level of miR-16, and compared using the Mann-Whitney U test.
Aim
To present selective arterial embolization with N-2-butyl Cyanoacrylate for the palliative and/or adjuvant treatment of painful bone metastases not primarily amenable to surgery.
Material and Methods
From January 2003 to December 2009, 243 patients (148 men and 95 women; age range, 20-87 years) with painful bone metastases were treated with N-2-butyl Cyanoacrylate. Overall, 309 embolizations were performed;
56 patients had more than one embolization. Embolizations were performed in the pelvis (168 procedures), in the spine (83 procedures), in the upper limb (13 procedures), in the lower limb (38 procedures) and in the thoracic cage (21 procedures). Primary cancer included urogenital, breast, gastrointestinal, thyroid, lung, musculoskeletal, skin, nerve and unknown origin.
Renal cell carcinoma was the most commonly treated tumour. In all patients, selective embolization was performed by transfemoral catheterization.
Background
It is common practice nowadays to treat patients with metastatic epidural spinal cord compression (MESCC) surgically. Extend and type of surgery should be in proper relation to the expected survival time of the patient. It is still difficult to predict patient's survival time and different scoring systems are used. Reliable prediction of survival is mandatory, in that way adjustable surgical treatment can be established.
Aim
Evaluating potential prognostic factors for survival after surgery for MESCC.
Aim
The aim of this study was to assess the financial implications of managing skeletal metastases in a tertiary hospital and explore its impact on the provision of acute care trauma services.
Methods
We identified 47 patients, surgically treated for skeletal metastases over one-year period. Data were collected on demographics, primary tumour, the bone involved, surgery performed, the type of prosthesis used, length of surgery, hospital stay and the exact indication for orthopaedic intervention. The cost incurred was calculated from the cost of the prosthesis implanted, the number of theatre-sessions utilised and the number of inpatient hospital days.
Aim and purpose
The clinical management of osteosarcoma differs significantly from that of chondrosarcoma;
Therefore it is extremely important to diagnose these two types of bone tumour accurately. In the absence of a specific marker, differential diagnosis by histochemistry is sometimes impossible, especially between chondroblastic osteosarcoma and conventional chondrosarcoma. The aim of the study was to find an useful diagnostic marker, simple to use for distinguishes chondroblastic osteosarcoma from conventional chondrosarcoma.
Method
We analysed 165 bone sarcomas by immunohistochemical staining of tissue microarrays for expression of the galectin-1 (GAL1) lectin and by Western Blot experiments.
Besides conventional chondrosarcoma, several rare chondrosarcoma subtypes are described, comprising about 15% of all chondrosarcomas. Clear cell chondrosarcoma (CCS) is a low-grade malignant tumour, often recurring after curettage, and showing overall survival of about 85%. Mesenchymal chondrosarcoma (MCS) is a highly malignant tumour occurring in bone and soft tissue of relatively young patients. The tumour shows differentiated cartilage mixed with undifferentiated small round cells. It often metastasises and shows a 5-year overall survival of 55%. Dedifferentiated chondrosarcoma (DDCS) is a tumour containing a high-grade non-cartilaginous sarcoma (DD), and a usually low-grade malignant cartilage-forming tumour (WD).
The prognosis is poor. The lack of efficacious treatment of these rare tumours emphasises the need to learn more about their characteristics and to unravel potential targets for therapy.
We constructed tissue microarrays (TMAs) with 2mm cores of 45 DDCS (WD and DD), 24 CCS, and 25 MCS, in triplicate.
Using immunohistochemistry, we investigated protein expression of estrogen-signaling molecules, growth plate-signaling molecules, and other molecules which might be potential targets for therapy. In addition, we gathered genomic information using Agilent 44K oligo arrays.
30% of the WD components were positive for Cox-2. Almost all others were negative. For Bcl2, 88% of the small cells and 32% of the cartilage in MCS were positive. In CCS, WD, and DD 48%, 4%, and 12% were positive, respectively. We demonstrated the presence of ESR1 and aromatase protein in the majority of tumours in all subtypes. Using array CGH, we observed similar aberrations in the two components of DDCS, with additional aberrations in the DD.
Celecoxib treatment is not recommended, as most of the tumours are negative for Cox-2. However, the presence of ESR1 and aromatase support a possible effect of anti-estrogen treatment in all subtypes, and application of Bcl2 inhibitors might chemosensitise MCS.
Chondrosarcomas are malignant hyaline cartilage tumours of bone. They are clinically resistant to conventional chemo- and radiotherapy and the underlying mechanism is poorly studied. Chemoresistance is a multifactorial process and the inaccessibility due to abundant hyaline cartilaginous matrix surrounding the cells, presence of multi-drug resistance pumps, and expression of anti-apoptotic proteins such as BCL2, have been suggested. Our aim was to study chemoresistance mechanisms in chondrosarcoma.
We first studied the sensitivity of chondrosarcoma cell lines (SW1353, CH2879, JJ012, OUMS27) and 2 primary cultures for doxorubicin and cisplatin. We used a 3D pellet model of CH2879 to study doxorubicin incorporation. To investigate whether chondrosarcoma cells could be resensitised to chemotherapy we tested the BH3 mimetic ABT737 inhibiting anti-apoptotic BCL2 family proteins. Cell viability was assessed using a WST assay for mitochondrial activity.
Dose response curves showed that chondrosarcoma cell lines and cultures are partially resistant to doxorubicin, while primary cultures were completely resistant to cisplatin. In 3D cell pellets, with morphology strongly resembling high grade chondrosarcoma, doxorubicin incorporation was confirmed. Chondrosarcoma cells responded to ABT737 with a >60% reduction in cell viability at high concentrations (25μM). Combination treatment allowing 2 days between ABT737 and chemotherapy addition led to a complete reduction of cell viability in all cell cultures.
In conclusion, chondrosarcoma cell lines show a partial response to doxorubicin and less response to cisplatin. The incorporation of doxorubicin in the cells in a 3D pellet model indicates that resistance is not caused by inaccessibility of the cells for the drugs nor by multi-drug resistance pump activity. By combining BCL2 inhibition with Doxorubicin treatment, a complete reduction of cell viability was obtained. This suggests that BCL2 overexpression plays an important role in chemoresistance of chondrosarcoma, and turning on the apoptotic machinery by BCL 2 inhibition can render them chemosensitive.
Aim
Assess symptoms and diagnostic problems of chest wall chondrosarcoma and factors related to long doctor's delay.
Methods
The material included all 106 consecutive patients with chondrosarcoma of the chest wall diagnosed in Sweden 1980-2002. Pathological specimens were re-evaluated and graded by the Scandinavian Sarcoma Group pathology board. Files from the very first medical visit for symptoms related to the chondrosarcoma were traced and used to characterise the initial symptoms, calculate patient's and doctor's delay and to identify factors contributing to the delays
Aim
Assess the oncological and clinical outcomes associated with intralesional curettage, phenol and bone grafting of the lesions.
Method
A retrospective study was performed using data from the Leiden University Medical Center. Ninety patients with low grade central chondrosarcoma of long bones and small tubular bones were treated using phenol and ethanol as adjuvant therapy after intralesional curettage. Standard clinical follow-up contained regular visits to the orthopaedic department, physical examination and radiological follow-up with plain X-rays and dynamic Gadolineum-enhanced MRI scans.
Background
Cryosurgery is a well established modality in the treatment of benign aggressive and low grade malignant tumours. In this setting it allows for intra-lesional resection and preservation of function without compromising oncological outcome. Here we present the outcome of 87 patients treated with cryosurgery for low-grade chondrosarcoma of bone.
Materials and methods
87 patients were treated between 1988 and 2005. The mean age was 51 years (range, 8-77 years), and included 47 females and 40 males. Minimal follow-up was two years. Patients were treated for lesions of the distal femur (n = 30), proximal humerus (n = 33), proximal femur (n = 5), proximal tibia (n = 10), and the remaining sites included the iliac bone, distal tibia, forearm, carpal and tarsal bones (n=10). Patients were treated with intralesional curettage through a cortical window, adjuvant burr drilling, cryotherpay and reconstruction with cement or bone graft and hardware fixation when that was clinically indicated.
Aim
We investigated low grade intramedullary chondrosarcomas to see if curettage and cementation remains a strong alternative treatment to local resection.
Methods
39 patients with biopsy proven low grade chondrosarcoma treated with curettage and cementation in our clinic between 1993-2009. 32 were females and 7 were males. Mean age was 44. Mean follow up was 40.5 months. Anatomical localizations were 16 proximal humerus and 16 proximal femur, 6 distal femur and 1 proximal tibia. All patients had plain X-ray, CT scan, Tc99 bone scan and MRI before open biopsy. 28 patients had frozen intraoperative biopsy. Histological diagnosis were grade I chondrosarcoma in all our patients. Curettage followed by high speed burr and cementation with high viscosity bone cement was applied without any internal fixation. Active physiotherapy began after 2 days of the operation and full weight bearing is permitted at about 2 weeks later.
Aim
To review the first 50 cases, looking at survivorship of the irradiated autograft, complications and functional outcomes in a wide range of bony malignancies and anatomical locations.
Methods
50 patients underwent en-bloc resection, extracorporeal irradiation with 50 Gy, and re-implantation for limb salvage between August 1996 and June 2003. Case notes and patients were reviewed.
Introduction
We analyzed the results of extracorporeal radiated (ECRT) autogenous tumour bone for reconstruction of diaphyseal defects after tumour resection at our institute.
Methods
Sixteen diaphyseal bone tumours operated between March 2006 to March 2008 were reconstructed with ECRT bone after appropriate oncologic resection. These included 10 cases of Ewing's sarcoma, 5 of Osteosarcoma and 1 Adamantinoma. Nine involved femur, 5 tibia and 2 humerus. Suitable internal stabilisation (14 cases plate fixation, 2 intramedullary nails) was used after re-implanting ECRT bone. Average resection length was 18.9 cm (range, 11 to 30 cm).
Aim
To identify factors leading to the success or failure of extracorporeal irradiation and re-implantation of bone (ECIR).
Method
Review of experience of this technique since 1996 documenting successes and failures.
The purpose of this study was to compare the outcome, complications and survival of the three most commonly used surgical reconstructions of the proximal humerus in adult patients after trans-articular tumour resection.
Method
Between1985 and 2005 thirty-eight consecutive proximal humeral reconstructions using either, allograft-prosthesis composite (n=10), osteoarticular allograft (n=13) or a modular tumour prosthesis (n=14), were performed in our clinic. Their mean follow-up was ten years (nine months to 25 years). Of these, twenty-seven were disease free at latest follow-up (Mean follow-up 16.8 years) and ten had died of disease (4.2 years). Complications and implant survival with revision surgery as end-point are presented for the total group of patients, functional scores for surviving patients only.
Results
The endoprosthetic group presented the smallest complication rate of 21%, compared to 40% in the allograftprosthesis- composite and 62% in the osteoarticular allograft group. Only one revision was performed in the endoprosthetic group, in a case of shoulder instability. Infection after revision (n=3), pseudoarthrosis (n=2), fracture of the allograft (n=3), and shoulder instability (n=4) were major complications of allograft use in general. Kaplan-Meier-analysis showed a significantly better implant survival for the endoprosthetic group (log-rank p=0.002). At final follow-up the MusculoSkeletal Tumour Society scores averaged at; 72% for the allograft-prosthetic-composite (n=7, mean follow-up 19 years), 76% for the osteoarticular allograft (n=3, 16 years), and 77% for the endoprosthetic reconstruction (n=10, 6 years) groups.
Several methods have been used for proximal humeral reconstruction following tumour resection. None of these modalities allow the patient to regain his normal shoulder range of motion. Moreover, every modality has its advantages and disadvantages.
The aim of this study was to compare the functional outcome of 2 reconstructive modalities that we are using in our institution for proximal humeral reconstruction; endoprosthesis and shoulder arthrodesis using a vascularised autograft This study included 48 patients diagnosed with malignant or benign aggressive tumours that required resection of their proximal humerus. They were divided into 2 groups according to the method of reconstruction. Group 1 included 22 patients with an average age of 20 years were reconstructed by shoulder arthrodesis using a free vascularised fibular graft (6) or a pedicled scapular crest graft (16). Group 2 included 26 patients with an average age of 26 years were reconstructed with an endoprosthesis.
In group 1 the average follow up period was 88 months (range 12 to 184 months). The average functional outcome (according to the MSTS scoring system) was 25 points (range 19 – 28). The average abduction and forward flexion range of motion (scapulothoracic) was 40 degrees (range 20 -60). Complications included failed fixation (2), non union (1), infection (1) and temporary radial nerve palsy (2). In group 2 the average follow up period was 36 months (range 12 – 110). The average functional outcome was 24 points (range 20 – 27). The average abduction and forward flexion range of motion was 40 (range 30 –70). Complications included sublaxation (2), loosening (1) and infection (1).
Reconstruction of the proximal humerus by arthrodesis or endoprosthesis yield similar functional outcome. Although endoprosthesis is a much more expensive modality, it does not provide any superior functional outcome over shoulder arthrodesis.
Aim
The aim of this study was to analyze our results using a modular endoprosthetic replacement system (MUTARS) for bone tumours of the proximal humerus.
Methods
Thirty-nine patients were treated with a MUTARS endoprosthesis of the proximal humerus. Mean follow-up was 38 months (3-138 months). Most operations were necessitated by metastasis (n=30); surgery for a primary tumour (n=9) was less frequent. The Enneking score and the active ranges of motion for shoulder flexion, abduction, and external rotation were recorded. Complete refixation of the rotator cuff was possible in 23 cases. Radiographs also were obtained.
In proximal humerus reconstructions, osteoarticular massive allograft (OA) allows a biologic reattachment of tendineous structures of the host providing stability and functional recovery. Allograft-prosthesis composites (APC) are more technically demanding, but functional advantages with new prosthetic design are expected with lower fracture and failure rate with time. We compared the outcome of patients treated with OA reconstruction (group A) and patients treated with an APC (group B) after humerus resection for bone tumours.
Thirty six patients treated between 1996 and 2009 were included in the study (18 group A; 18 group B). The diagnosis was a malignant bone tumour in 28 cases, an aggressive benign bone tumour in 6 and a bone metastasis in 2. Three total humerus resections were performed (two in group A and one in group B). Three different type of prosthesis were used (conventional, reverse and resurfacing). In group A, at an average follow-up of 66 months (2-116), 16 patients were continuously disease free.
Ten patients (56%) had no complication; in 6 cases (33%) we observed a fracture of the graft and in 3 cases (17%) a pseudoarthrosis. In group B, at an average follow up of 44 months (3-164), 16 patients were continuously disease free.
Thirteen patients (72%) had no complication, in 2 cases (11%) stem loosening, in 2 cases (11%) dislocation, in 1 case pseudoarthrosis and in 1 case resorption and detachment of allograft's great tuberosity was observed. Functional outcome was evaluated using MSTS scoring system: a mean score of 24 (13-30) in group A and 23 (15-27) in group B was observed.
In our experience, proximal humerus APC showed functional results comparable to OA allograft with lower complication rate.
In conclusion, in biologic reconstruction of the proximal humerus, APC seems to provide a more reliable solution than OA allograft at long term
Aim
Local treatment of Ewing sarcoma of the hip bones and sacrum remains one of the most difficult tasks in the treatment of bone sarcomas. We investigated the difference between size, local treatment and overall survival in Ewing sarcoma of the sacrum and hip bones.
Methods
Patients with Ewing sarcoma of the hip bones or sacrum, diagnosed between 1986 and 2009, were identified through the Scandinavian Sarcoma Group registry. Data regarding tumour size, local treatment (radiation or surgery), local recurrence, surgical margin, metastatic disease, and overall survival were analyzed and compared between the two locations (hip bone or sacrum).
Aim
To determine the overall survival of patients with Pelvic Ewing's Sarcoma treated in our unit and to identify prognostic factors in pelvic primaries that could be used to select patients who would most likely benefit from high intensity treatment.
Method
Between 1977 and 2009, 80 male and 66 female patients aged 2 to 60 (mean, 18) years with Pelvic Ewing's Sarcomas were retrospectively reviewed from the Royal Orthopaedic Hospital Oncology Service Registry. Treatments included surgery, radiotherapy, chemotherapy, or any of them in combination. Event-free (from presentation to recurrence) and overall (from presentation to death/latest follow-up) survival rates were calculated using the Kaplan- Meier method.
Influence of various factors (age at diagnosis, gender, tumour site, metastasis at presentation, surgery (and surgical margins), radiotherapy, and type of treatment on survival was assessed using SPSS 14.0 statistical software.
Aim
The saddle prosthesis was originally developed for reconstruction of large acetabular defects in hip revision arthroplasty. Later on the saddle prosthesis was also used for hip reconstruction after resection of peri-acetabular tumours. In case of patient survival a long-term good hip function is required of the saddle prosthesis. The goal of this study is the measurement of long-term clinical results of saddle prosthesis after reconstruction of peri-acetabular tumours.
Method
Between 1987 and 2003 a total of 17 patients were treated in the Leiden University Medical Center with saddle prosthesis after resection of peri-acetabular tumours (12 chondrosarcoma, 3 osteosarcoma, 1 malignant fibrous histiocytoma, 1 metastasis). 11 of the 17 patients died, the mean survival was 37 months (range 2-59 months), and 6 patients were still alive (follow-up 12.1 year, range 8.3–16.8 year). The outcome was measured with the SF-36 questionnaire, the Toronto Extrimity Salvage Score (TESS) and the Musculo Skeletal Tumour Society (MSTS) score. In 1 patient the saddle prosthesis was removed already after 3 months because of luxation and infection.
Introduction
The pelvis has always been a difficult area for surgeons, with high complication rates from surgery and the perception of poor oncological outcomes. The aim of the study was to look at the surgical and oncological outcomes of pelvic tumours treated at our centre.
Methods
From the 3100 primary bone tumours seen at the ROH. Information was retrieved on 539 patients seen with a primary bone tumour of the pelvis. The demographic details, oncological and surgical outcomes were reviewed.
Aim
In osteosarcoma, local control of the tumour is absolutely critical otherwise the chances of long term survival are <10% and may effectively approach zero. Radiotherapy is used in case of non-resectable tumours. Histone deacetylase inhibitors (HDACIs) can enhance the sensitivity of cells to photon radiation (XRT) by altering numerous molecular pathways. Therefore, we investigated the effect of the pan-HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) on radiation response in osteosarcoma (OS) and rhabdomyosarcoma (RMS) cell lines.
Methods
Clonogenic survival, cell cycle analysis, apoptosis and gammaH2AX phosphorylation as a marker of DNA double strand breaks (DSBs) were examined in two OS (KHOS-24OS, SAOS2) and two RMS (A-204, RD) cell lines treated with SAHA alone and SAHA plus XRT, respectively. Protein expression was investigated via immunoblot analysis, cell cycle analysis, measurement of apoptosis and gammaH2AX expression were performed using flow cytometry.
Aim
To compare two consecutive treatment programs in metastatic osteosarcoma at presentation.
Methods
Between 1987 and 1999 treatment of stage IIIB osteosarcoma included induction chemotherapy (CHT) which consisted in 3-5 cycles of intra-arterial doxorubicin (DOX) 75 mg/m2 or cis-platin (CDDP) 120 mg/m2, surgery or definitive local radiation therapy (RT) for primary and adjuvant CHT with DOX, CDDP or HDMTX. Thirty nine patients were included in this protocol. Since 2000 a more intensive induction CHT protocol was adopted. It consisted in 4 cycles of DOX 90 mg/m2 +CDDP 120 mg/m2 (24 patients) or DOX 60 mg/m2 +CDDP 120 mg/m2+Ifosfamide (IFO) 6 g/m2 (7 patients). Adjuvant chemotherapy included DOX, CDDP, IFO or VP-16. Residual lung deposits were removed at the end of adjuvant treatment.
Aim
Ten years ago at the EMSOS 2000 meeting we have presented our experience concerning the non-surgical treatment of stage IIB osteosarcoma of extremities. The purpose of study was to evaluate long-term results and complications related to this non-standard and controversial treatment modality.
Methods
Since 1988 definitive radiation gamma therapy (RT) in the median dose of 60 Gy was administrated to 36 patients who refused surgery after preoperative chemotherapy. Until 1999 induction consisted in 3-5 cycles of intra-arterial doxorubicin (DOX) 75 mg/m2 or cis-platin (CDDP) 120 mg/m2. Since 2000 induction comprised 4 cycles of DOX 90 mg/m2+CDDP 120 mg/m2 intra-arterially. Tumour response before local treatment was assessed non-invasively by means of X-ray, CT, MRI, angiography, 3-phase bone scans and alkaline phosphatase measurement. The end-points were overall (OS), metastases free (MFS) and local progression free (LPFS) survival at 10 years.
Aim
The use of megaprostheses for knee reconstruction after distal femur resection in young bone sarcoma patients has become popular since early ′80. The authors reviewed their experience with different distal femur megaprostheses in children.
Method
Clinico-radiographic evolution in a consecutive series of 113 children, that had implanted below age 15 (range 6-14) a distal femur megaprosthesis in the period 1984-2007, was analized. A modular implant was used in 97 cases with uncemented femoral stem (three different models along the period). The implant presented fixed-hinge joint in 78 cases while rotating-hinge knee was utilized in 19 cases. In 39 cases the fixed-hinge joint had a tibial component with a polished stem to allow the residual growth of proximal tibia; in two cases a mechanically extendable prosthesis was used. A custom-made noninvasive extendable prosthesis with cemented femoral stem and smooth uncemented tibial stem was used in 15 cases since 2002. Radiological and functional results were analysed and a statistical comparison of implant outcome according different stems was obtained.
Aim
The percentage of adolescents and young adults with sarcoma enrolled in multicenter clinical trials is reportedly much lower than that of younger children. We intended to determine if this remained true despite the availability of a study open to patients up to the age of 40 years
Method
Review of interim recruitment and randomization rates in a large randomized multinational trial for resectable osteosarcoma, EURAMOS-1, jointly performed by COG, COSS, EOI, and SSG, within ECT-EUROCORES. Randomization scheduled after preoperative chemotherapy and definitive surgery of the primary tumour.
Neoadjuvant chemotherapy for osteosarcoma improves outcomes for the majority, but if the chemotherapy does not work then the dilemma often arises as to whether to do limb salvage with a marginal (or worse) margin of excision or to do an amputation. If limb salvage is carried out with a close margin, does post operative radiotherapy make any difference? This study aims to address these questions.
Method
All patients with limb osteosarcoma, no metastases, a poor response to chemotherapy and either a marginal excision or primary amputation were identified from a prospective database. This group were investigated in terms of overall survival and local control.
Results
There were 182 patients in this category of whom 60 had an amputation, 105 limb salvage with marginal margins and 17 with an intralesional margin. Local recurrence (LR) arose in 41% of those with an intralesional margin, 22% of those with a marginal margin and 13% of those with an amputation. Radiotherapy was used in 21 of the 122 patients and the risk of LR was the same as in those who did not have radiotherapy. Neither age nor sex of the patient, size or site of the tumour affected the risk of LR. The overall survival for this group was 42% at 10 years. The survival was best in those with marginal margins (38%) than those with an amputation (28%) and worst for those with an intralesional margin (20%). Survival was worst in those who did develop LR, but no worse than in those having amputation
Introduction
Recently a great deal of interest has emerged in new techniques for resection of bone tumours, such as the use of computer guided surgery, joint sparing prostheses and epiphysiolysis. However, all the techniques may require narrower margins at resection than the traditional Enneking wide margins. The aim of the study was to look at the effect of width and tissue at surgical margins, together with the use of adjuvant therapy on locally recurrent disease and disease free survival.
Methods
The quality in terms of precise distance (mm) and tissue has been regularly reported by our pathologists for 5 years, prior to this it was reported as wide, marginal or intralesional. It is known from previous studies that 90% of locally recurrent disease for osteosarcoma and Ewings occurs within 2 years from surgery. Therefore all primary bone sarcomas of the pelvis and appendicular skeleton that underwent surgery between 1/1/2005 and 1/1/2008 were entered into the study group, giving at least 2 years follow up. The pathology records were reviewed and the quality of the margins and percentage tumour necrosis were recorded. Those patients who had suffered local or distal disease relapse or died were highlighted. Analysis was undertaken by Kaplan Meier survival curves with univariate and multivariate analysis.
Expandable prostheses were designed to allow progressive growth after tumour resection in children. The aim of this study was to report the late results of the non-invasive growing prostheses designed by A Soubeyran (Phenix prosthesis or Wright Repiphysis).
From 1994 to January 2006, 27 children aged 4 to 12 (mean 8.5), underwent a resection of the knee for a bone tumour, with reconstruction by a non invasive expandable prosthesis. There were 16 boys and 11 girls. The tumours were 25 osteosarcomas and 2 Ewing tumours. All patients received pre and post-operative chemotherapy. There were 18 distal femur, 7 proximal tibia, and 2 femur + tibia resections.
There were different successive designs based on the same electro-magnetic growing mechanism using a pre bent spring, released by eating in an induction coil.
After, 7.2 years mean follow-up (4 months to 15 years), 20 patients had no evidence of disease and 7 were deceased. Two with a local recurrence were amputated. Mean lengthening was 5.1 centimeters (0 to 8), after 3 to 11 lengthening procedures. Mean limb-length discrepancy was 1.8 cm. Two patients had a secondary infection. Eleven had a revision for arthrofibrosis. All surviving patients were revised to a conventional hinged prosthesis. The mean MSTS functional score of the definitive prosthesis was 82% (63 to 96%).
Theses prostheses showed many mechanical complications as loosening, fracture of the growing mechanism, and arthrofibrosis. The positive outcome was the possibility to perform a progressive lengthening, without surgery limiting the risk of infection. Theses prostheses should be considered as temporary until reconstruction with a conventional hinged prosthesis. Patients with multiple revisions had a tendency to show less favourable late functional results than with primary implanted hinged prosthesis.
Aim
We present the greatest study of patients with proximal fibula resection. Moreover we describe a new classification system for tumour resection of the proximal fibula independent of the tumour dignity.
Method
In 57 patients the functional and clinical outcome was evaluated. The follow up ranged between 6 months and 22.2 years (median 7.2 years). Indicationfor surgery was in 10 cases benign tumours and in 47 cases malignant tumours. In 32 patients a resection of the peroneal with resulting peroneal palsy was necessary.
For many surgeons amputation is the usual treatment in sarcoma of the foot. The aim of our study was to report the functional and oncologic results of treatment in 54 sarcomas of the foot to assess if conservative treatment was acceptable
We retrospectively reviewed the records of 54 patients with sarcomas of the foot, aged 6 to 50 (mean 17), 30 females and 26 males. At time of referral, 18 had a local recurrence of a previous inadequate treatment. There were 27 soft tissue sarcomas (STS: 10 synovial sarcomas, 6 rhadomyosarcomas, 1 liposarcomas and 10 others) and 27 bone tumours (16 Ewing's, 8 chondrosarcomas, 3 osteosarcomas). Toes tumours were excluded, 18 tumours involved the metatarsal, 12 the plantar soft tissues, 11 the calcaneum, 3 the talus, 2 the midtarsal bones.
Surgery consisted in 19 resection without reconstruction, 21 resections with bone reconstruction, 9 partial amputations of the foot, and 6 trans tibial amputations.
In 34 cases surgical margins were adequate (R0), in 13 patients resection was inadequate (9 R1 and 4 R2). In 7 cases the margins were not assessed.
After a 5.5 years average follow-up (3m to 17y), 31 patients had no evidence of disease, 8 were in second remission, 4 had an evolutive disease and 11 were deceased. The mean MSTS score was 26/30 (31 cases).
In conclusion, a conservative treatment is feasible in metatarsal bones with skin coverage by flap if necessary. In STS adequate margins are difficult to achieve with a high rate of local recurrence. In calcaneus and talus, a conservative treatment is possible in tumours limited to bone after good response to chemotherapy. In other cases conservative treatment is debatable because amputation gives excellent functional results.
The outcome for patients with Ewing's sarcoma recurrence is poor. Local recurrences occur in 8%-25%of these patients. The aim of the study was to analyze the patients who had a local recurrence to identify factors predicting the local recurrence and if it could be prevented
Methods
A retrospective analysis of 650 patients who had a diagnosis of Ewing's sarcoma treated between 1975 and 2009 at a single institution was performed and 64 patients (10%) who had a local recurrence were identified and analysed.
Results
Fifteen patients had metastases at diagnosis.20 patients had chemotherapy and radiotherapy only while 44 had chemotherapy and surgery +/− post op radiotherapy. Thirteen patients who were suitable for post –operative radiotherapy could not receive the treatment due to various reasons like biological reconstruction. The estimated 5 years survival for the patients was 15%. The risk of local recurrence is higher if the tumour is located in the axial skeleton, treatment with chemotherapy and radiotherapy alone [location and size of the tumour precluding surgery]. The risk of local recurrence is higher if the tumour was in the fibula or radius. One out of three patients who have good response to chemotherapy still went on to develop a LR. The use of biological reconstruction and younger age group often resulted in deferral of post-operative radiotherapy. Location and type of treatment can predict LR. Surgery with clear margins and post-operative radiotherapy given when indicated may reduce the incidence of LR.
Introduction
Bone tumours rarely involve the joint surface as cartilage is thought to be a good barrier to tumour spread. When the tumour does cross the surface the surgeon is faced with the dilemma of whether to amputate the limb, resect it without reconstruction or reconstruct with an implant. This paper aims to investigate the oncological and functional outcomes of patients undergoing an extra-articular resection and reconstruction with an endoprosthesis.
Method
3100 patients have been seen in ROH with primary bone tumours. Patients were identified who had an extra-articular resection considered pre-operatively and the notes and imaging was reviewed. This group was subdivided into a group who did have an extra-articular resection (EAR) and those who either had an amputation or traditional through joint resection. The outcomes of the three groups (group 1 = no joint involvement, group 2 = EAR considered but not done and group 3 = EAR) were then compared in terms of oncological outcome, surgical margins and complications.
Aim
To evaluate outcome and complications of knee arthrodesis with a modular prosthetic system (MUTARS(r) Implantcast), as primary and revision implants in musculoskeletal oncology.
Method
Between 1975 and 2009, 24 prostheses were used for knee arthrodesis. Nineteen in oncologic cases: 6 osteosarcomas, chondrosarcoma, synovial sarcoma and metastatic carcinoma 3 each, 2 pigmented villonodular synovitis (PVNS), malignant fibrous hystiocitoma and giant cell tumour 1 each. Patients were grouped into: A) primary implants, B) revision implants. Group A included 9 patients: 8 arthrodeses after extra-articular resection with major soft tissue removal, 1 after primary resection following multiple excisions of locally recurrent PVNS. Group B included 15 patients: 12 arthrodeses for infection (5 infected TKAs, 7 infected megaprostheses), 2 for failures of temporary arthodesis with Kuntscher nail and cement, 1 for recurrent chondrosarcoma in previous arthrodesis.
Aim
To compare the functional outcome of proximal femoral reconstruction using endoprosthetic replacement and hip arthrodesis using a vascularised fibular graft
Material and Methods
The study included thirty-five patients who had proximal femoral reconstruction following resection of a malignant bone tumour. Patients were divided into 2 groups according to the reconstructive modality used. Group 1 (15 patients) reconstructed by hip arthrodesis using a vascularised fibular graft. Group 2 (20 patients) reconstructed by endoprosthesis. The mean age of group I was 14.9 years (range, 7-25). 8 patients had Ewing's sarcoma, 5 osteogenic sarcoma, and 2 chondrosarcoma. In group 2, the mean age was 35 years (range, 14-61). Eight patients had osteogenic sarcoma, 2 chondrosarcoma, 2 Ewing's sarcoma, 1 lymphoma, 1 MFH, 1 synovial sarcoma, 1 parosteal osteosarcoma, and 4 metastatic carcinomas.
Aim
Giant cell tumour (GCT) of bone is a benign but locally aggressive tumour. Although topical adjuvants have been used in the past, local recurrence following intralesional excision of GCT of bone continues to remain a problem. The use of bisphosphonates as an anti-osteoclastic agent in the management of osteolytic bone metastases is well accepted. Therefore our study aims to retrospectively demonstrate whether the administration of bisphosphonate as an adjuvant can control aggressive local recurrence of GCT and prevent wide resections of bones or amputations.
Method
A retrospective study was performed between 2004 and 2010. 6 patients were diagnosed with aggressive local recurrence of appendicular GCT. All patients were treated for the primary tumour by surgical curettage and cryoablation followed by cementation or biological reconstruction. In 5 patients the tumour was located in the distal radius and in one in the first metacarpal bone. All recurrences were in the bone with large soft-tissue extension. After histological diagnosis – by CT core needle biopsy – the patients were treated by intravenous bisphosphonate, followed by clinical & radiological assessments.
Aim
The first osseointegrated transfemoral amputation prosthesis operation was performed in Gothenburg in 1990. The aim is improving quality of life for patients who cannot use conventional socket prosthesis. In 1999 the prospective OPRA-study (Osseointegrated Prosthesis for Rehabiliation of Amputees) was initiated with standardized surgery, equipment and rehabilitation program.
Method
The surgery consists of a two-stage procedure. At the primary surgery (S1), a titanium screw (the fixture) is inserted into the remaining diaphyseal bone. The fixture is 80 mm long with a diameter of 16–20 mm (+0.5 mm increments). The patient is hospitalized 5-7 days.
At the secondary surgery (S2), six months later, an abutment is inserted into the fixture. The abutment has a hexagonal press-fitting into the fixture and is secured by an abutment screw. The patient remains hospitalized 10–12 days. Gradual increase of load and activity is initiated over a 6 month period.
Prognostic stratification of patients with non-metastatic osteosarcoma may improve the clinical management and the design of clinical trials.
Data from 773 patients [median age 15 years (3-40)] treated at our Institute from 1983 to 2000 with high-dose methotrexate, cisplatin, doxorubicin and ifosfamide (neoadjuvant chemotherapy) were analyzed. After multivariate analysis including age, site, tumour volume (cut-off 200 mL), serum LDH and Alkaline Phosphatase (SAP), histology (osteoblastic and chondroblastic vs others), high LDH and SAP, osteoblastic and chondroblastic histotypes resulted independent prognostic factors of DFS.
Patients were grouped according to a score from 0 (absence) to 3 (one to 3 adverse factors). The scoring system was implemented by the addition of PgP expression and grade of chemotherapy-induced necrosis.
A score of 0, 1, 2, 3 was given to 14%, 38%, 32% and 16% of patients respectively.10-year DFS was 80% (95%CI 72-89) for score of 0, 58% (95%CI 52-64) for 1, 53% (95%CI 46-59) for 2 and 40% (95%CI 32-50) for 3 (p= 0.001). PgP expression (168 patients) identified patients with 100% probability of DFS (score of 0 and negative PgP) and patients with 18% (95%CI 52-64) DFS (score of 3 and positive PgP).
Good (GR) and poor responder (PR) patients had the same probability of DFS in case of score of 0 [GR82% (95% CI 72-91), PR79% (95% CI 65-93)] and score of 3 [GR43% (95% CI 32-55) PR36% (95% CI 21-51)]. Different probability of DFS in case of score of 1 [GR64% (95% CI 57-72) PR47% (95% CI 36-59)] and score of 2 [GR63% (95% CI 55-71) PR36% (95% CI 21-51)].
It is possible to stratify outcomes of patients with non metastatic osteosarcoma of the extremity by means of a simple score based on easily available clinical parameters. This scoring system is worth to be validated on larger series.
There is currently no standard follow up protocol for patients who have been diagnosed with and treated for high-grade osteosarcoma. We therefore investigated the possibility of creating a risk based follow-up protocol for patients with primary osteosarcomas.
313 patients diagnosed with primary osteosarcomas were studied. The identified risk factors for local recurrence included poor necrosis, inadequate margins and high risk tumour site in the bone. The risk factors for metastases were poor necrosis, inadequate margins, extra-compartmental stage and tumour size ≥5cm.
The risk of local recurrence and/or metastases within three years of diagnosis increases as the number of risk factors increase. Patients were grouped according to their number of risk factors. The cumulative risk of metastases for patients with 0, 1, 2, 3 and 4 risk factors is 0%, 12%, 21%, 54% and 60% respectively (p=<0.0001). Risk of local recurrence for patients with 0, 1, 2 and 3 risk factors is 5%, 14%, 25% and 20% respectively (p=0.0025).
Our investigation shows that by grouping patients together according to their number of identified risk factors, it is possible to identify groups of patients that are most at risk. This information can be used to design an evidence based follow up protocol which would have important implications for clinical practice.
Aim
Preoperative serum CRP has been identified as an independent predictor in various malignancies. For osteosarcoma, however, the value of serological markers is unreliable. Aim of this study was to evaluate the prognostic power of preoperative CRP in patients with osteosarcoma.
Method
Out of our prospective database, 87 patients with osteosarcoma (43 female, 44 male with an average age of 20.4 years) have been identified with complete documentation of peri-operative CRP-levels, a minimum two year follow-up and after exclusion of concomitant infection, smoking-history or cardio-vascular disease. Pre-operative CRP before tumour resection was correlated with clinical and pathological factors, overall survival and infection rates in an uni- and multi-variate statistical model with and without landmark analysis.
Aim
To report late development of sarcomas on sites of previously curetted and grafted benign tumours. Rare cases of development of sarcomas in sites of previous benign lesions are documented, and the development is generally considered secondary to progression of benign lesions, even without radiotherapy.
Methods and Results
In our files, 12 cases curetted and grafted, without radiotherapy addition developed sarcomas from 6 to 28 years from curettage (median 18). Age at first diagnosis (9 GCT, 1 benign fibrous histiocytoma, ABC and solitary bone cyst) ranged from 13 to 55 (median 30). For all cases radiographic and clinic documentation was available. Histology was available for 7 of the benign lesions and for all malignant lesions. The type of bone used to fill cavities was autoplastic in 4 cases, homoplastic in 2 cases, homoplastic and tricalciumphosphate/hydrossiapatite in 1 case, autoplastic and homoplastic in 1 cases, heteroplastic in 1 case. In 3 cases the origin was not reported. Secondary sarcomas, all high grade, were 8 OS, 3 MFH, and 1 fibrosarcoma.
SSX was initially identified as a melanoma associated tumour antigen MEL2 and in the SS18/SSX fusion gene of synovial sarcoma. It consists of a family of nine, highly homologous X chromosome genes, being SSX1, SSX2 and SSX4 the most commonly expressed in tumours. In normal tissue, SSX expression is restricted to germ cells, trophoblasts, and mesenchymal stem cells. In malignant cells, SSX expression is over-represented in sarcomas. SSX expression is epigenetically regulated by methylation and histone deacetylation.
Aim
To investigate the oncogenic properties of SSX. Validate it as tumour target and identify lead compounds.
Methods
RNAi system for conditional silencing of SSX expression, Protein analysis and Mass Spec, PCR arrays, tumour xenographs and drug library screening.
Aim
Synovial sarcoma (SS) is a malignant soft tissue sarcoma with a poor prognosis because of late local recurrence and distant metastases. To our knowledge, no studies have minimum follow-up of 10 years that evaluate long-term outcomes for survivors.
Method
Data on 62 patients who had been treated for SS from 1968 to 1999 were studied retrospectively in a multicenter study. The following parameters were examined for their potential prognostic value: age at diagnosis, sex, tumour site and size, histology, histological grade, fusion type (SYT-SSX1 vs. SYT-SSX2), and surgical margin status. Mean follow-up of living patients was 17.2 years, and of dead patients 7.7 years.
The rising incidence of atraumatic fractures in patients either with Ewing's sarcoma or osteosarcoma years after chemotherapy revealed a growing population of childhood cancer survivors with a decreased bone mineral density (BMD) possibly due to a long-term effect of the chemotherapy. Therefore we started to screen our patients below 50y of age who were treated for bone malignancies between 1994 and 2009.
The first series of measurements included 15 patients – eight Ewing's sarcoma, three female and five male, with a mean age of 18y (±13SD), and seven osteosarcoma, two female and five male, with a mean age of 19y(±9SD). We screened the patients for deficits in their bone status using DEXA (dual-energy-x-ray-absorptiometry) to gain the T-and Z-Scores of the proximal femur and the lumbal spine. Additionally we took blood samples for endocrinological analysis and utilised a questionnaire to scan the patient's liefestyle. The mean time between diagnosis and investigation was 95months (±79SD) in Ewing's sarcoma and 105months (±54 SD) in osteosarcoma.
The results of the age and gender matched lumbal measurement (Z-Score) of the Ewing's sarcoma patients showed a reduction of the BMD in six cases (6/8), including three times osteopenia (3/8) and two times osteoporosis (2/8). The osteosarcoma patients presented a BMD-decline in four cases (4/7) with two times osteopenia (2/7) and one osteoporosis (1/7).
In the proximal femur six Ewing's sarcoma (6/8) and six osteosarcoma patients (6/7) showed a BMD-decrease including three osteopenic (3/8) and one osteoporotic (1/8) Ewing's sarcoma and four osteopenic osteosarcoma (4/7). We found two cases of pathologic fractures (2/15), one Ewing's sarcoma 29 months after diagnosis with a fracture of the distal femur and the proximal Tibia (1/8) and one osteosarcoma with a fractured distal femur after 72 months (1/7).
As presented in our case series osteoporosis after chemotherapy is an underestimated long-term effect of the chemotherapeutic treatment. In our series BMD-reduction seems to be independent of tumour-type and chemotherapeutic agent like MTX.
Aim
Patients treated with limb salvage surgery for bone sarcomas of the extremities (upper and lower) may have physical disability as a result of treatment. Goal of this study was to evaluate the quality of life after treatment (chemotherapy and conservative surgery) at long term.
Method
208 patients resected for a bone sarcoma and with prosthetic reconstruction (45 in the upper and 163 in the lower limb) were evaluated. Assessment of results was done using the Karnofsky Scale (K.S.). Patients were followed in the clinic and functional results assessed according to the Musculoskeletal Tumour Society (MSTS) system. Moreover the Toronto Extremity Salvage Score questionnaire (TESS) was mailed to 144 patients.
Introduction
The aim of this study was to investigate the results of a series of cases from a single institution with respect to local disease control and patient survival to determine prognostic factors.
Methods
Electronic patient records were reviewed on all patients with STS between February 1963 and January 2007. 2445 patients had over 30 types of STS. 1639 (67%) had not received any treatment prior to presentation, however, 770 patients (32%) had undergone a previous attempted excision. Survival analyses were done using Kaplan Meier and Cox regression analyses, however, for prognostic factor analysis, only patients presenting without prior treatment were included.
Aim
Purpose of this study was to review a single Institution experience and results of management of extraskeletal osteosarcoma (OGS), with emphasis on the role of combined treatment consisting of surgery and adjuvant chemotherapy.
Method
Retrospective study of 48 patients observed 1966- 2007 was undertaken: 36 patients were managed at our Institution while 12 cases were consultations and not included in this study. Clinico-pathologic features and details of treatment of all 36 patients were correlated with outcome. Updated follow-up was available in all patients.
Aim
While the association of surgery and radiation therapy in high grade Soft Tissue Sarcoma (STS) of extremities is considered the “golden standard”, there is not international agreement regarding type, timing, overall dose of radiation, and size, site and histology of tumours to be irradiated. A similar consideration is about low grade STS. The aim of our paper is critically reconsider our experience, trough a retrospective analysis of 15 years experience. This in order to propose a perspective protocol of treatment of high and low grade STS, in order to minimize the late complication rate.
Method
From January 1994 to June 2009 we have operated in our Centre 976 patients affected by STS of extremities and superficial trunk. They were 741 High grade STS (76%), and 235 Low grade STS (24%). The most represented histotype was Liposarcoma (239) followed by Leiomyosarcoma (150) and synovial sarcoma (94). Regarding tumour site, upper limb was involved in 255 cases, lower limb in 679, superficial trunk in 42; regarding tumor size, 323 where less than 5 cm, 386 where between 5 and 10 cm and 267 where more than 10 cm. Radiation therapy was utilized in 447 cases (46%): 83 patients had a low grade STS, 364 a high grade STS.
Aim
was to analyze infections after bone tumour surgery.
Method
1463 patients treated from 1976 to 2007 were analized: 1036 with resection and prostheses in the lower limbs, 344 with resection and prostheses in the upper limbs, 83 with surgery for sacral tumours. Infections were analyzed for time of occurrence (“postoperative” in the first 4 weeks from surgery, “early” within 6 months, and “late” after 6 months), microbic agents, treatment, outcome.
