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Bone & Joint Research
Vol. 10, Issue 9 | Pages 602 - 610
24 Sep 2021
Tsoi KM Gokgoz N Darville-O'Quinn P Prochazka P Malekoltojari A Griffin AM Ferguson PC Wunder JS Andrulis IL

Aims

Cell-free DNA (cfDNA) and circulating tumour DNA (ctDNA) are used for prognostication and monitoring in patients with carcinomas, but their utility is unclear in sarcomas. The objectives of this pilot study were to explore the prognostic significance of cfDNA and investigate whether tumour-specific alterations can be detected in the circulation of sarcoma patients.

Methods

Matched tumour and blood were collected from 64 sarcoma patients (n = 70 samples) prior to resection of the primary tumour (n = 57) or disease recurrence (n = 7). DNA was isolated from plasma, quantified, and analyzed for cfDNA. A subset of cases (n = 6) underwent whole exome sequencing to identify tumour-specific alterations used to detect ctDNA using digital droplet polymerase chain reaction (ddPCR).


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVIII | Pages 141 - 141
1 Sep 2012
Biau DJ Ferguson P Chung P Turcotte R Isler M Riad S Griffin AM Catton C O'Sullivan B Wunder JS
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Purpose

Due to the aging population, an increasing proportion of elderly patients with soft tissue sarcoma are presenting to cancer centers. This population appears to have a worse prognosis but the reasons for this has not been studied in depth. The purpose of this study is to examine the effect of age on the outcome of patients with extremity and trunk soft tissue sarcoma.

Method

This is a multicenter study including 2071 patients with median age at operation of 57 years (1st quartile–3rd quartile: 42–70). The endpoints considered were local recurrence and metastasis with death as a competing event. Cox proportional hazards models were used to estimate hazard ratios across the age ranges with and without adjustment for known confounding factors.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVIII | Pages 208 - 208
1 Sep 2012
Weiss KR Biau DJ Bhumbra R Griffin AM Ferguson P Wunder JS
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Purpose

Ewings sarcoma (EWS) is the second most common primary malignancy of bone. Five-year survival ranges between 50 and 70% for patients who present with localized disease. EWS occurs in both axial and appendicular locations. The prognostic importance of anatomic location (axial vs. appendicular) is unclear. The purpose of this study is to report a single institution experience in the management of patients with EWS, and to investigate anatomic location as a prognostic factor.

Method

After ethics board approval, we searched our prospective sarcoma database for all EWS patients treated between 1989 and 2007. Sixty-seven patients with adequate follow-up were identified and records were reviewed. Axial bone EWS was defined as originating from the spine, sacrum, pelvis, scapula, clavicle, or rib cage. Appendicular bone EWS was defined as disease from any bone in the extremities. Axial soft tissue EWS was defined as originating in the head, neck, or torso. Appendicular soft tissue EWS originated from the extremeties. Sixty-six (99%) patients received chemotherapy. Definitive local treatment was by surgical resection whenever possible (n=44). Radiation therapy (RT) was used for unresectable lesions (n=10) or to treat positive margins (n=10). The primary outcome measure was overall survival (OS) measured from the date of diagnosis to the date of death or last follow-up and estimated using the Kaplan-Meier method. Univariate and multivariate analyses were performed. Besides anatomic location, the variables of tumor size, metastases at diagnosis, treatment with radiation, and surgical margins were studied.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVIII | Pages 144 - 144
1 Sep 2012
Biau DJ Ferguson P Chung P Riad S Griffin AM Catton C O'Sullivan B Wunder JS
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Purpose

The main predictors in the literature of local control for patients operated on for a soft tissue sarcoma are age, local presentation status, depth, grade, size, surgical margins and radiation. However, due to the competing effect of death (patients who die are withdrawn from the risk of local recurrence), the influence of these predictors on the cumulative probabilities may have been misinterpreted so far. The objective of the study was to interpret the influence of known predictors of local recurrence in a competing risks setting.

Method

This single center study included 1519 patients operated on for a localized soft tissue sarcoma of the extremity or trunk. Cox models were used to estimate the cause specific hazard of known predictors on local recurrence. Cumulative incidences were estimated in a competing risks scenario.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_IV | Pages 573 - 573
1 Nov 2011
Ferguson P Fallis CE Griffin AM Deheshi B Wunder JS
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Purpose: Patients are often referred to tertiary care centers after unplanned excision of soft tissue sarcomas. In situations where the tumour is small and superficial, the situation can often easily be salvaged by re-excision of the tumour bed. However, if the original tumour is large, deep to fascia or directly adjacent to bone or neurovascular structures, the salvage procedure often becomes more complex and morbid. The purpose of this study is to evaluate the effect of unplanned excision of “high-risk” soft tissue sarcomas on patient outcome.

Method: We reviewed our prospectively collected sarcoma database from 1989 to 2006. Patients who underwent definitive resection of a soft tissue sarcoma at our centre were included. Patients were divided into 2 groups based on whether or not they had undergone initial unplanned resection of their tumour prior to referral to our centre for definitive management. Low risk patients who had tumours that were less than 5 cm in diameter, superficial to fascia, and not overlying bone or neurovascular structures were excluded.

Results: A total of 1034 patients met inclusion criteria. Of these, 385 (37%) patients had undergone an unplanned excision prior to referral, while 649 (63%) patients were referred to our centre with an intact tumour without prior unplanned excision. There was a higher percentage of high grade (61% vs. 50%) and deep tumours (88% vs. 65%) in the unplanned excision group, but the mean tumour diameter was smaller in the unplanned excision group (5.9 cm) compared to the control group (10.6 cm). There was no difference between the groups in terms of rate of amputation, necessity for flaps for coverage, and local recurrence-free survival. Complications were more common in the control group (34%) than the unplanned excision group (20%, p< 0.0005, Chi-square). 5-year overall (p< 0.00005, log rank) and metastasis-free (p< 0.00005, log rank) survival were higher in the unplanned excision group. There was no difference in TESS, MSTS87 or MSTS93 functional outcome scores between the groups.

Conclusion: Patients referred to a tertiary sarcoma centre after unplanned resection of a soft tissue sarcoma can still be salvaged with appropriate multidisciplinary care. Patients referred after unplanned excision appear to fare at least as well as those initially resected at our centre, and fare better in terms of some outcomes studied. The majority of this difference can likely be explained by significant differences in important prognostic factors such as grade, size and depth between the unplanned excision group and control group initially managed at our centre. Patients referred after unplanned excisions appear not to have as dismal an outcome as has been previously reported.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 64 - 64
1 Mar 2010
Gortzak Y Mahendra A Griffin AM Wunder JS Ferguson PC
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Objectives: A stable shoulder is essential for proper elbow and hand function after oncologic resection of the shoulder girdle. We describe a surgical technique for replacing the shoulder joint capsule using synthetic mesh after resections of the shoulder girdle that resulted in gross intraoperative instability of the shoulder joint.

Methods: 68 patients who underwent shoulder girdle resection between 1989 and 2006 were identified in our prospective database. This report focuses on nine patients whose shoulder joint was reconstructed with synthetic mesh. All patients were followed on a 3 monthly basis. Shoulder joint instability was determined from clinical records, database and radiographs.

Results: Nine patients underwent shoulder joint reconstruction with synthetic mesh. One patient underwent a shoulder disarticulation within 30 days of the index surgery and was excluded from this rapport.

No dislocations were noted during follow-up (range 3–48 months). Radiographs revealed an average vertical displacement of the humeral head compared to its original position of 0.7 cm (range 0–1.7 cm). There were two surgical complications. In one patient the humeral prosthesis migrated proximally and eroded through the skin requiring additional surgery. In another case erosion of the distal clavicle was noted. This was biopsied and foreign body reaction identified.

Conclusions: Joint instability following major resections of the shoulder girdle is a source of morbidity and affects the function of the salvaged limb. Synthetic capsular reconstruction using Marlex mesh is a useful adjunct in patients where insufficient shoulder musculature and joint capsule remains after resection to allow for stable suspension of the upper limb.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 63 - 63
1 Mar 2010
Gortzak Y Mahendra A Griffin AM Lockwood G Wang Y Deheshi B Wunder JS Ferguson PC
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Objectives: To formulate a scoring system enabling decision making for prophylactic stabilization of the femur following surgical resection of a soft tissue sarcoma (STS) of the thigh.

Methods: A logistic regression model was developed using patient variables collected from a prospective database. The test group included 22 patients with radiation-related pathological femur fracture following surgery and radiation for a thigh STS. The control group of 79 patients had similar treatment but without a fracture. No patients received chemotherapy. Mean follow-up was 8.6 years. Variables examined were: Age (< 49, 50–70, > 70 years), gender, tumor size (0–7, 8–14, > 14 cm), radiation dose (low=5000 cGy, high> 6000 cGy), extent of periosteal stripping (< 10, 10–20, > 20 cm) and thigh compartment (posterior, adductor, anterior). A score was assigned to each variable category based on the coefficients obtained in the logistic regression model.

Results: Based on the regression model and an optimal cut-point, the ability to predict radiation associated fracture risk was 91% sensitive and 86% specific. The area under the Receiver Operating Characteristic (ROC) curve was 0.9, which supports this model as a very accurate predictor.

Conclusions: Radiation-related femur fractures following combined surgery and radiation treatment for STS are uncommon, but are difficult to manage and their non-union rate is extremely high. These results suggest that it is possible to predict radiation-associated pathological fracture risk with high sensitivity and specificity. This would allow identification of high risk patients and treatment with prophylactic IM nail stabilization. Presentation of this model as a clinical nomogram will facilitate its clinical use.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 64 - 64
1 Mar 2010
Mahendra A Griffin AM Yu C Gortzak Y Bell Ferguson PC Wunder JS Davis A
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Objectives: To investigate whether components of MSTS-87 (Pain, ROM, Strength, Stability, Deformity, Acceptance and Function) correlate with function as measured by TESS following endoprosthetic replacement (EPR) for patients with bone sarcoma.

Methods: 255 patients with extremity bone sarcoma treated by resection & EPR were identified from a prospective database. From this group we investigated 111 patients with primary bone sarcoma with > 2 years follow up, evaluated by both MSTS-87 & TESS, no local recurrence, metastasis or major complication for at least 2 years prior to the follow-up. Upper extremity patients were excluded due to small numbers. We examined the influence of patient demographics and tumour characteristics on functional outcome scores. Correlation between MSTS-87 & TESS was performed using linear regression analysis.

Results: Age, gender, tumour size, anatomical site, chemotherapy treatment and presence of pathological fracture did not significantly correlate with TESS. Linear regression analysis of MSTS-87 individual criteria and total score revealed that only pain, ROM and function helped explain the TESS score (p < 0.05) while strength, stability, deformity & acceptance had no significant effect on overall functional outcome.

Conclusions: Of the seven MSTS-87 variables, only pain, ROM and function significantly correlate with overall functional outcome as measured by TESS following EPR for bone sarcoma. This suggests that patients with decreased strength, stability, deformity and acceptance as defined by MSTS-87 scores, may still adapt well with good overall functional outcomes.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_I | Pages 64 - 65
1 Mar 2010
Mahendra A Gortzak Y Griffin AM Wunder JS Ferguson PC
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Objectives: Well fixed, ingrown stems in patients with infected, uncemented knee tumor prostheses are difficult to remove. We have shown that it?s not necessary to remove them for infection control. We describe a technique for intraoperative fabrication of antibiotic-impregnated temporary cement prostheses using rush pin endoskeleton during first stage revision of infected, uncemented knee tumor prostheses.

Methods: We used this method in 7 patients with infected uncemented tumor prostheses around the knee. Two patients are awaiting second stage procedures. Surgery involved removing exchangeable components and retaining well-ingrown stemmed intramedullary components. Spacers were made of Rush pins that were bent and placed through hinge of retained component to allow knee movement. Antibiotic impregnated cement was placed around pins.

Results: This method allowed partial weight-bearing, knee movement, stability and pain control between first and second stages. In 4/5 patients infection was eradicated. Second-stage reimplantations were accomplished successfully in 3/5 patients with no obvious metal wear. Mean interval between the 2 stages was 12 weeks. One patient had residual infection requiring amputation and one patient did not agree to further surgery. Overall functional outcome following revision was TESS 82.3/100, MSTS93 73.3/100, MSTS87 23.3/35.

Conclusions: The technique allows maintenance of length, stability and knee joint movement, thus subsequent revision becomes technically simpler. Cement construct has large surface area to maximize antibiotic elution. This method has advantages of low cost, availability of numerous pin dimensions, which allows a custom component. Although there is no obvious wear, this remains a potential concern at articulation of rush rods and retained component.


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_II | Pages 253 - 253
1 May 2009
Saidi K London O Bell RS Griffin AM Saidi K Wunder JS
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Radiation induced pathologic fractures present a difficult problem for musculoskeletal oncologists. The purpose of this study was to determine the outcomes of management of radiation-induced pathologic fractures in a group of patients who had previously undergone combined management of extremity soft tissue sarcoma.

A review of our retrospective database was undertaken. From 1986 to present, thirty-two patients with soft tissue sarcomas were found to have radiation induced pathologic fractures. The records of these patients were reviewed for patient demographics, tumour size and anatomic site, presence of periosteal stripping at time of surgery, radiation dose, time to fracture, fracture treatment and fracture outcome.

There were twenty-three females and nine males with a mean age of sixty-three (range thirty-six to eighty-nine) years. Fractures occurred at a mean of forty-five months after resection of the sarcoma (range three to one hundred and fifty months). Anatomic distribution of fractures were : proximal femur(twelve), femoral diaphysis (eight), distal femur (two) tibia (five), acetabulum (two), metatarsal (two) and patella (one). Periosteal stripping was performed in half of the patients. Twenty-three patients had received high dose radiation (6600Gy). Seven fractures were managed conservatively while twenty-five were treated surgically. Only eleven of the thirty-two fractures united. Six patients underwent amputation, three for local recurrence and three for non-union of their fracture. Eight patients ultimately underwent arthroplasty, while seven patients have persistent non-unions. In the proximal femur, only three out of twelve fractures healed while six patients eventually underwent arthroplasty and three continue to have non-unions. Of eight femoral diaphyseal fractures, only one united. Patients who eventually underwent prosthetic replacement had good function and pain relief.

Radiation induced pathologic fractures are a difficult clinical problem. In particular patients with fractures in the proximal femur often undergo multiple attempts at fixation before definitive management with resection and endoprosthetic replacement. Fractures of the femoral diaphysis rarely heal despite aggressive surgical management. Primary arthroplasty may be considered in some patients as an alternative to fixation in radiation-induced pathologic fractures of the femur in order to avoid long term morbidity and repeated operations.


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_II | Pages 111 - 111
1 Feb 2003
Abudu A Driver N Wunder JS Griffin AM Pearce D O’Sullivan B Catton CN Bell RS Davis AM
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812 consecutive patients with soft tissue sarcoma of the extremity were studied to compare the characteristics and outcome of patients who had primary amputations and limb preserving surgery.

Patients with primary amputations were more likely to have metastases at presentation, high-grade tumours, larger tumours and were older.

The most frequent indications for primary amputation were tumour excision which would result in inadequate function and large extracompartmental tumours with composite tissue involvement including major vessels, nerves and bone.

The requirement for primary amputation was a poor prognostic factor independent of tumour grade, tumour size and patients’ age.


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_II | Pages 111 - 111
1 Feb 2003
Gerrand CH Wunder JS Kandel RA O’Sullivan B Catton CN Bell RS Griffin AM Davis AM
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To determine if rates of local recurrence and metastasis differ in upper versus lower extremity sarcomas.

Prospectively collected data relating to patients undergoing limb-sparing surgery for extremity soft tissue sarcoma between January 1986 and April 1997 were analysed. Local recurrence-free and metastasis-free rates were calculated using the method of Kaplan and Meier. Univariate and multivariate analyses of potential predictive factors were evaluated with the log-rank test and the Cox proportional hazards model.

Of 480 eligible patients, 48 (10. 0%) had a local recurrence and 131 (27. 3%) developed metastases. Median follow-up of survivors was 4. 8 years (0. 1 to 12. 9). There were 139 upper and 341 lower extremity tumours. Upper extremity tumours were more often treated by unplanned excision before referral (89 vs 160, p< 0. 001) and were smaller (6. 0cm vs 9. 3cm, p< 0. 000). Lower extremity tumours were more often deep to or involving the investing fascia (280 vs. 97, p< 0. 003). The distribution of histological types differed in each extremity. Fewer upper extremity tumours were treated with adjuvant radiotherapy (98 vs. 289, p< 0. 000).

The 5-year local recurrence-free rate was 82% in the upper and 93% in the lower extremity (p< 0. 002). Local recurrence was predicted by surgical margin status (hazard ratio 3. 16, p< 0. 000) but not extremity (p=0. 127) or unplanned excision before referral (p=0. 868).

The 5-year metastasis-free rate was 82% in the upper and 69% in the lower extremity (p< 0. 013). Metastasis was predicted by high histological grade (hazard ratio 17. 28, p< 0. 000), tumour size in cm (hazard ratio 1. 05, p< 0. 001) and deep location (hazard ratio 1. 93, p< 0. 028) but not by extremity (p=0. 211).

Local recurrence is more frequent after treatment for upper compared with lower extremity sarcomas. Variation in the use of radiotherapy and differences in histological type may be contributory. Metastasis is more frequent after treatment for lower extremity sarcomas because tumours tend to be large and deep.