Objective. Sarcomas are a rare group of tumours, which pose numerous problems regarding correct diagnosis and appropriate management. This study aimed to examine whether symptom duration and tumour size at diagnosis have changed over time, using size and symptom duration as methods of comparison. Methods. All patients diagnosed with sarcoma were identified retrospectively from a prospective database from 1963 to 2005. Demographic data concerning age at diagnosis, sex and diagnosis were recorded. Data were also collected on duration of symptoms and size of tumour at diagnosis. Symptom duration is defined as the length of time the patient was experiencing symptoms for until the date of diagnosis. Changes in size and symptom duration over time were compared by grouping date of diagnosis into time periods and comparing them against each other using non-parametric statistical analysis. Results. 4560 met our inclusion and exclusion criteria, with 2492 Bone Sarcomas (BS) and 2068 Soft Tissue Sarcomas (STS). Overall analysis of both BS and STS showed that size at diagnosis has decreased and symptom duration has increased. Analysis of STS showed that size has decreased over time, particularly following the introduction of referral guidelines in 1999 (median size pre 99 = 10cm, post = 8cm, Mann-Whitney-U test p=0.000 to 3 sig. fig.), but symptom duration has remained unaltered over time. Duration of symptoms reported for BS has significantly increased over time; however, size at diagnosis has remained unchanged over time. Conclusions. It appears from this study that STS are being diagnosed more quickly and that this is most likely due to the introduction of specific STS guidelines in 1999. This result is particularly heartening, and should encourage further promotion of such guidelines. Awareness of BS still appears to be low as size at diagnosis remains unchanged over time

The purpose of this study is to present a series of soft tissue sarcomas requiring complex vascular reconstructions, and to describe their management and outcomes. Soft tissue sarcomas are rare mesodermal malignancies accounting for approximately 1% of all cancers diagnosed annually. Sarcomas involving the pelvis and extremities are of particular interest to the orthopaedic surgeon. Tumours that encase and invade large calibre vascular structures present a major surgical challenge in terms of safety of excision with acceptability of surgical margins. Technical advances in the fields of both orthopaedic and vascular surgery have resulted in a trend towards limb salvage with vascular reconstruction in preference to amputation. Limb-salvage surgery is now feasible due to the variety of reconstructive options available to the surgeon. Nevertheless, surgery with concomitant vascular reconstruction is associated with higher rates of complications including infection and amputation. We present a case series of soft tissue sarcomas with vascular compromise, requiring resection and vascular reconstruction. We treated four patients (n = 4, three females, and one male) with soft tissue masses, which were found to involve local vascular structures. Histology revealed leiomyosarcoma (n = 2) and alveolar soft part sarcomas (n = 2). Both synthetic graft and autogenous graft (long saphenous vein) techniques were utilised. Arterial reconstruction was undertaken in all cases. Venous reconstruction was performed in one case. One patient required graft thrombectomy at one month post-operatively for thrombosis. We present a series of complex tumour cases with concomitant vascular reconstructions drawn from our institution's experience as a national tertiary referral sarcoma service

Abstract

Radiation induced sarcoma of bone is a rare but challenging disease process associated with a poor prognosis. To date, series are limited by small patient numbers; data to inform prognosis and the optimal management for these patients is needed. We hypothesized that patients with radiation-induced pelvic bone sarcomas would have worse surgical, oncologic, and functional outcomes than patients diagnosed with primary pelvic bone sarcomas

This was a multi-institution, comparative cohort analysis. A retrospective chart review was performed of all patients diagnosed with a radiation-induced pelvic and sacral bone sarcoma between January 1st, 1985 and January 1st, 2020 (defined as a histologically confirmed bone sarcoma of the pelvis in a previously irradiated field with a minimum 3-year interval between radiation and sarcoma diagnosis). We also identified a comparison group including all patients diagnosed with a primary pelvic osteosarcoma/spindle cell sarcoma of bone (i.e. eligible for osteosarcoma-type chemotherapy) during the same time interval. The primary outcome measure was disease-free and overall survival.

We identified 85 patients with primary osteosarcoma of the pelvis (POP) and 39 patients with confirmed radiation induced sarcoma of the bony pelvis (RISB) undergoing surgical resection. Patients with RISB were older than patients with POP (50.5 years vs. 36.5 years, p67.7% of patients with POP underwent limb salvage as compared to 77% of patients with RISB; the type of surgery was not different between groups (p=.0.24). There was no difference in the rate of margin positive surgery for RISB vs. POP (21.1% vs. 14.1%, p=0.16). For patients undergoing surgical resection, the rate of surgical complications was high, with more RISB patients experiencing complications (79.5%) than POP patients (64.7%); this approached statistical significance (p=0.09).

15.4% of patients with RISB died perioperative period (within 90 days of surgery) as compared to 3.5% of patients with POP (p= 0.02). For patients undergoing surgical resection, 5-year OS was significantly worse for patients with RISB vs. POP (27.3% vs. 47.7%, p=0.02). When considering only patients without metastatic disease at presentation, a significant difference in 5-year survival remains for patients with RISB vs. POP (28.6% vs. 50%, p=0.03) was a trend towards poorer 5-year DFS for patients with RISB vs. POP (30% vs. 47.5%), though this did not achieve statistical significance (p=0.09).

POP and RISB represent challenging disease processes and the oncologic outcomes are similarly poor between the two; however, the disease course for patients with RISB appears to be worse overall. While surgery can result in a favorable outcome for a small subset of patients, surgical treatment is fraught with complications.

Lymph node metastasis are a rare occurrence in soft tissue sarcomas of the extremity, arising in less than 5% of patients. Few studies have evaluated the prognosis and survival of patients with a lymph node metastasis. Early reports compared lymph node involvement to lung metastasis, while others suggested a slightly better outcome. The purpose of this study was to evaluate the impact of lymph node metastasis on patient survival and to investigate the histologic and clinical features associated with lymph node involvement.

A retrospective review was done of the prospectively collected soft tissue sarcoma database at our institution. Two thousand forty-five patients had surgery for soft tissue sarcoma of an extremity between January 1986 and August 2017. Included patients either presented with a synchronous lymph node metastasis or were diagnosed with a lymph node metastasis after their initial treatment. Demographic, treatment, and outcome data for patients with lymph node involvement were obtained from the clinical and radiographic records.

Lymph node metastases were identified as palpable adenopathy by physical examination and were further characterized on cross-sectional imaging by computed tomography (CT) or magnetic resonance imaging (MRI) scans. All cases were confirmed by pathologic examination of biopsy specimens. A pathologist with expertise in sarcoma determined the histologic type and graded tumors as 1, 2, or 3.

One hundred eighteen patients with a mean age of 55.7 (SD=18.9) were included in our study. Seventy-two (61.3%) out of 119 patients were male. Thirty six patients (57.1%) had lymph node involvement at diagnosis. The mean follow-up from the date of the first surgery was 56.3 months. The most common histological diagnoses were Malignant fibrous histiocytoma (35) and liposarcoma (12). Ninety eight patients (89%) underwent surgical treatment of the lymph node metastasis while 21 (17.6%) were treated with chemotherapy and/or radiation therapy. The mean survival was 52.6 months (range 1–307).

Our results suggest that patients with a lymph node metastasis have a better prognosis than previously described. Their overall survival is superior to patients diagnosed with lung metastasis. A signifant proportion of patients may expect long term survival after surgical excision of lymph node metastasis. Furthermore, our study also indicates that different histological subtypes such as liposarcoma or malignant peripheral nerve sheath tumor (MPNST) may also be responsible for lymph node metastasis. Additional studies to further improve the treatment of soft tissue sarcoma nodal metastasis are warranted.

Paediatric bone sarcomas around the knee are often amenable to either endoprosthetic reconstruction or rotationplasty. Cosmesis and durability dramatically distinguish these two options, although patient-reported functional satisfaction has been similar among survivors. However, the impact on oncological and surgical outcomes for these approaches has not been directly compared.

We retrospectively reviewed all wide resections for bone sarcoma of the distal femur or proximal tibia that were reconstructed either with an endoprosthesis or by rotationplasty at our institution between June 2004 and December 2014 with a minimum two year follow-up. Pertinent demographic information, surgical and oncological outcomes were reviewed. Survival analysis was performed using the Kaplan-Meier method with statistical significance set at p<0.05.

Thirty eight patients with primary sarcomas around the knee underwent wide resection and either endoprosthetic reconstruction (n=19) or rotationplasty (n=19). Groups were comparable in terms of demographic parameters and systemic tumour burden at presentation. We found that selection of endoprosthetic reconstruction versus rotationplasty did not impact overall survival for the entire patient cohort but was significant in subgroup analysis. Two-year overall survival was 86.7% and 85.6% in the endoprosthesis and rotationplasty groups, respectively (p=0.33). When only patients with greater than 90% chemotherapy-induced necrosis were considered, overall survival was significantly better in the rotationplasty versus endoprosthesis groups (100% vs. 72.9% at two years, p=0.013). Similarly, while event-free survival was not affected by reconstruction method (60.2% vs. 73.3% at two years for endoprosthesis vs rotationplasty, p=0.27), there was a trend towards lower local recurrence in rotationplasty patients (p=0.07). When surgical outcomes were considered, a higher complication rate was seen in patients that received an endoprosthesis compared to those who underwent rotationplasty. Including all reasons for re-operation, 78.9% (n=15) of the endoprosthesis patients required a minimum of one additional surgery compared with only 26.3% (n=5) among rotationplasty patients (p=0.003). The most common reasons for re-operation in endoprosthesis patients were wound breakdown/infection (n=6), limb length discrepancy (n=6) and periprosthetic fracture (n=2). Excluding limb length equalisation procedures, the average time to re-operation in this patient population was 5.6 months (range 1 week to 23 months). Similarly, the most common reason for a secondary procedure in rotationplasty patients was wound breakdown/infection, although only two patients experienced this complication. Average time to re-operation in this group was 23.8 months (range 5 to 49 months).

Endoprosthetic reconstruction and rotationplasty are both viable limb-salvage options following wide resection of high-grade bony sarcomas located around the knee in the paediatric population. Endoprosthetic reconstruction is associated with a higher complication rate and may negatively impact local recurrence. Study of a larger number of patients is needed to determine whether the reconstructive choice affects survival.

Aim

To identify patient, tumour or treatment factors that influence outcome in patients with radiation induced sarcoma of bone.

Purpose

Rotationplasty was first described in 1930 by Borggreve for treatment of limb shortening with knee ankylosis after tuberculosis. In 1948, Van Nes described its use for management of congenital defects of the femur and in the 1980s, Kotz and Salzer reported on patients with malignant bone tumors around the knee treated by rotationplasty as an alternative to above-knee amputation. Currently, rotationplasty is one of the options for surgical management of lower extremity bone sarcomas in skeletally immature patients but alternative limb salvage techniques, such as the use of expandable endoprosthesis, are also available. Despite rather satisfactory functional results have been uniformly associated with rotationplasty, concern still exists about the potential psychological impact of the new body imagerelated to the strange appearance of the rotated limb. Results of rotationplasty for sarcomas of the distal femur over a 20-year period were analyzed, focusing on long-term survival, function, quality of life and mental health.

Pelvic sarcomas are uncommon and pose considerable challenges to surgery. Tumour resections necessarily lead to destabilisation of the pelvic ring and this is believed to have a negative impact on lower limb function. Depending on the type of resection, there are a number of innovative reconstructions that can re-establish pelvic stability and optimise limb function.

Conservative approaches that ignore pelvic instability are also employed and these may be applied following type I, I+II, II+III, I+II+III resections. These reconstructions include ilio-femoral and ilio-ischial athrodeses. On occasions, no reconstruction may be employed.

Outcomes following minimal reconstructive efforts remain unclear. Reconstructing the pelvic ring may not be necessary in all cases to achieve satisfactory function

Soft tissue sarcomas (STS) arising in the adductor compartment of the thigh are frequently large before clinical detection, posing particular challenges with surgical resection and associated with a high risk of wound complications. This study compares oncological and functional outcomes and complications following treatment of adductor compartment soft tissue sarcomas from three international centres with different treatment philosophies.

184 patients with new primary, non-metastatic, deep STS in the adductor compartment diagnosed between 1990 and 2001 were identified from the centres' local databases. The Toronto Extremity Salvage Score (TESS) was used to assess function in patients.

There were 94 male and 90 female patients, with ages ranging from 13 to 88 years (median age 57 years). The period of follow-up ranged from 1 to 162 months. The overall survival was 65% at 5 years and related to grade and size of the tumour. There was no difference in overall survival or systemic relapse between the three centres. There was however a significant difference in local control (28% LR in centre 1 compared to 10% in centre 2 and 5% in centre 3, which appeared to be principally related to the use of radiotherapy and surgical margins.)

66 patients (36%) from the three centres developed wound complications post-operatively and it was shown to be associated with high grade and large tumours (>10cm).

Functional scores averaged 78% but were significantly worse for patients with wound complications or high-grade tumours; however, they were not affected by timing of radiotherapy or use of prophylactic free muscle flaps.

This is quite an innovative study that should lead to a multicentre validation trial. We have developed an FDG-PET/MRI texture-based model for the prediction of lung metastases (LM) in newly diagnosed patients with soft-tissue sarcomas (STSs) using retrospective analysis. In this work, we assess the model performance using a new prospective STS cohort. We also investigate whether incorporating hypoxia and perfusion biomarkers derived from FMISO-PET and DCE-MRI scans can further enhance the predictive power of the model.

A total of 66 patients with histologically confirmed STSs were used in this study and divided into two groups: a retrospective cohort of 51 patients (19 LM) used for training the model, and a prospective cohort of 15 patients (two patients with LM, one patient with bone metastases and suspicious lung nodules) for testing the model. In the training phase, a model of four texture features characterising tumour sub-region size and intensity heterogeneities was developed for LM prediction from pre-treatment FDG-PET and MRI scans (T1-weighted, T2-weighted with fat saturation) of the retrospective cohort, using imbalance-adjusted bootstrap statistical resampling and logistic regression multivariable modeling. In the testing phase, this multivariable model was applied to predict the distant metastasis status of the prospective cohort. The predictive power of the obtained model response was assessed using the area under the receiver-operating characteristic curve (AUC). In the exploratory phase of the study, we extracted two heterogeneity metrics from the prospective cohort: the area under the intensity-volume histogram of pre-treatment DCE-MRI volume transfer constant parametric maps and FMISO-PET hypoxia maps (AU-IVH-Ktrans, AU-IVH-FMISO). The impact of the addition of these two individual metrics to the texture-based model response obtained in the testing phase was first investigated using Spearman's correlation (rs), and lastly using logistic regression and leave-one-out cross-validation (LOO-CV) to account for overfitting bias.

First, the texture-based model reached an AUC of 0.94, a sensitivity of 1, a specificity of 0.83 and an accuracy of 0.87 when tested in the prospective cohort. In the exploratory phase, the addition of AU-IVH-FMISO did not improve predictive power, yielding a correlation of rs = −0.42 (p = 0.12) with lung metastases, and a relative change in validation AUC of 0% in comparison with the texture-based model response alone in LOO-CV experiments. In contrast, the addition of AU-IVH-Ktrans improved predictive power, yielding a correlation of rs = −0.54 (p = 0.04) with lung metastases, and a change in validation AUC of +10%.

Our results demonstrate that texture-based models extracted from pre-treatment FDG-PET and MRI anatomical scans could be successfully used to predict distant metastases in STS cancer. Our results also suggest that the addition of perfusion heterogeneity metrics may contribute to improving model prediction performance.

The use of peritumoral oedema on magnetic resonance (MR) imaging to predict soft tissue tumour grade is controversial. The clinical significance of oedema visualised on MR scans is poorly defined in the literature. We undertook this study to ascertain a diagnostic relationship between peritumoral oedema surrounding soft tissue sarcomas and the histological grade of the tumour.

One hundred and ten consecutive soft tissue tumours were extracted from the New Zealand Bone and Soft Tissue Tumour Registry. Key inclusion criteria were tumours deep to fascia, measuring more than 5cm in any dimension. Both benign and malignant sarcomas were included. MR scans and histology were reviewed, separately and in random order by a single author. Histology was graded as benign, low or high grade (based on the American Joint Committee on Cancer grading system).

Peritumoral oedema was defined as the increased signal intensity, on T2 or STIR images, immediately surrounding a discrete lesion. It was measured on two or more planes with the largest value used in diagnostic calculations. Oedema greater than or equal to 20mm was defined as a positive test result. Twenty five random scans were double read to ensure inter-observer reliability

Data was obtained for 83 tumours, 36 benign and 47 malignant (34 high grade and 13 low grade). The tumours in all groups were matched for size. The mean peritumoral oedema was 10.5mm for benign tumours, 20.6mm for low grade sarcomas (p<0.1), 28.1mm for high grade tumours (p<0.01) and 26.1mm if all malignant tumours were included as a single group (p<0.01). Using peritumoral oedema as a diagnostic test for tumour grade resulted in a specificity of 72%. The highest diagnostic ability was found when comparing benign to high grade tumours which yielded sensitivity of 59% and a positive likelihood ratio of 2.1. This data suggests a high false negative rate and that the test adds little to the diagnostic process.

To our knowledge this is the first study which assesses the diagnostic accuracy of peritumoral oedema to predict the histological grade of soft tissue sarcomas. Our results show a statistically significant difference, in surrounding peritumoral oedema, exists when comparing benign to high grade sarcomas and to all malignant tumours. This relationship is not apparent for low grade tumours. As a diagnostic test, using only peritumoral oedema to predict histological grade is unreliable.

Introduction

Historically, amputation or rotationplasty were the treatment of choice in skeletally immature patients. The introduction of expandable endoprostheses in the late 1980s offered the advantages of limb-salvage and limb length equality at skeletal maturity and a promising alternative with improved cosmetic results and immediate weight bearing.

Purpose

Mesenchymal stromal cells (MSCs) are an attractive choice for regenerative medicine. We previously showed that MSCs enhance wound healing in animals after radiotherapy. The effect of MSCs on tumor growth is not well understood. The potential use of MSCs to enhance wound healing after radiotherapy (RT) and resection of soft tissue sarcoma (STS) is dependent on a satisfactory safety profile to ensure that tumor proliferation does not occur and recurrence is not increased.

Sarcomas generally metastasize to the lung, while extra-pulmonary metastases are rare. However, they may occur more frequently in certain histological sub-types. Bone metastases from bone and soft tissue sarcomas account for a significant number of extra-pulmonary disease. Resection of lung metastases is widely accepted as therapeutic option to improve the survival of oligometastatic patients but there is currently no literature supporting curative surgical management of sarcoma bone metastases. Most are treated on a case-by-case basis, following multidisciplinary tumour boards recommendations. One study reported some success in controlling bone metastases using radiofrequency ablation. Our goal was to assess the impact of curative resection of bone metastases from soft tissue and bone sarcomas on oncologic outcomes. Extensive review of literature was done to evaluate epidemiological and outcomes of bone metastases in sarcoma. We examined our prospective database for all cases of bone metastases from sarcoma treated with surgical resection between 1990 and 2016. Epidemiology, pathology, metastatic status upon diagnosis, type of secondary relapses and their treatments were recorded. Overall survival and disease-free survival were calculated and compared to literature. Thirty-five patients were included (18 men, 17 women) with a mean age of 46 years. Fifteen were soft tissue (STS) and 20 were bone (BS) sarcomas. Most STS were fibrosarcomas, leiomyosarcomas or UPS while chondrosarcomas and osteosarcomas were the most frequent BS. Nine (60%) STS were grade 3, 4 (27%) grade 2 and one grade 1 (3%). Eight (23%) were metastatic upon diagnosis (6 lungs, 3 bone). Treatment of the primary tumour included wide excision with reconstruction and (neo)-adjuvant therapies as required. Margins were negative in 32 cases and micro-positive in 3 cases. Amputation occurred in 6 (17%) cases. Primary lung metastases were treated by thoracotomy and primary bone metastases by wide excision. First relapse occurred in bone in 19 cases (54%), lungs and bone in 7 cases, 5 in lungs and 4 in soft-tissues. Lung metastases were treated by thoracotomy and chemotherapy in 3 cases, chemotherapy alone in the remaining cases. Bone metastases were treated by wide resection-reconstruction in 24 cases, extensive curettage in 4. Soft tissue relapses were re-excised in 4 patients. Two amputations were required. All margins were negative except for the 4 treated by curettage. Fourteen second relapses occurred in bone, 7 were radically-excised and 2 curetted. At last follow-up, 6 patients were alive (overall survival of 17%), with a mean survival of 57 months, a median overall survival of 42.5 months and a median disease-free survival (DFS) of 17 months. Overall survival was 17%, compared to an 11% 10-year survival previously reported in metastatic sarcomas. Median disease-free survival was better in this study, compared to 10 months in literature, so as median OS (42.5 months vs 15). Three patients were alive with no evidence of disease. DFS, OS and median survival seemed to be improved by bone metastases wide excision and even if several recurrences occur, curative surgery with adjuvant therapies should be considered

Objective. To evaluate functional and oncological outcomes following sacral resection. Methods. A retrospective review was conducted of 97 sacral tumours referred to tertiary referral spinal or oncology unit between 2004 and 2009. Results. The study included Chordoma 26; Metastases 17; Chondrosarcoma 9; Osteosarcoma 8; Lymphoma 7; Ewing's Sarcoma 6; Giant Cell Tumours 5; Other Sarcomas 5; Aneurysmal Bone Cyst 4; Myeloma 4; Others 7. There were 61 males, 37 females with an average age of 47 (range 3-82). The average duration of pre-diagnosis symptoms was 13 months. In 17 cases the diagnosis was metastatic disease and these were excluded from further discussion. Of the remainder 36/81(44%) underwent surgery: 21 excision, 9 excision and instrumented stabilisation, and 6 curettage. Thirteen (16%) patients were inoperable: 8 advanced disease, 3 unable to establish local control and 2 cases of recurrence. Colostomy was performed in 11/21 (52%) patients who underwent excision. Deep wound infections in 6/21 (29%). No difference in infection rates between definitive surgery with or without colostomy – 3/11 (27%) vs 3/10 (30%). In the instrumented group, no colostomies were performed due to concerns about deep infection and none resulted (0/9). Radiological failure of stabilisation was noted in 7/9(78%). However, functionally, 3/9 (33%) were mobilising independently, 3/9 (33%) with crutches, 2/9 (22%) able to transfer and 1/9 (11%) undocumented. Mean follow-up was 25 months (range 0-70). Local recurrence in 9/36 (25%) of operated patients. Metastasis occurred in 4/36 (11%) and mortality 8/36 (22%) although follow-up period was noted to be short. Conclusions. Results are comparable with current literature. Mechanical stabilisation for extensive sacral lesions is challenging. Despite radiological failure in 7/9 instrumented stabilisations, patients were relatively asymptomatic and only 1/9 required revision stabilisation surgery. By design none had colostomies and there were no deep infections