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Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_13 | Pages 102 - 102
1 Dec 2022
Gundavda M Lazarides A Burke Z Griffin A Tsoi K Ferguson P Wunder JS
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Cartilage lesions vary in the spectrum from benign enchondromas to highly malignant dedifferentiated chondrosarcomas. From the treatment perspective, enchondromas are observed, Grade 1 chondrosarcomas are curetted like aggressive benign tumors, and rest are resected like other sarcomas. Although biopsy for tissue diagnosis is the gold standard for diagnosis and grade determination in chondrosarcoma, tumor heterogeneity limits the grading in patients following a biopsy. In the absence of definite pre-treatment grading, a surgeon is therefore often in a dilemma when deciding the best treatment option. Radiology has identified aggressive features and aggressiveness scores have been used to try and grade these tumors based on the imaging characteristics but there have been very few published reports with a uniform group and large number of cases to derive a consistent scoring and correlation.

The authors asked these study questions :(1) Does Radiology Aggressiveness and its Score correlate with the grade of chondrosarcoma? (2) Can a cut off Radiology Agressiveness Score value be used to guide the clinician and add value to needle biopsy information in offering histological grade dependent management?

A retrospective analysis of patients with long bone extremity intraosseous primary chondrosarcomas were correlated with the final histology grade for the operated patients and Radiological parameters with 9 parameters identified a priori and from published literature (radiology aggressiveness scores - RAS) were evaluated and tabulated. 137 patients were identified and 2 patients were eliminated for prior surgical intervention. All patients had tissue diagnosis available and pre-treatment local radiology investigations (radiographs and/or CT scans and MRI scans) to define the RAS parameters.

Spearman correlation has indicated that there was a significant positive association between RAS and final histology grading of long bone primary intraosseous chondrosarcomas. We expect higher RAS values will provide grading information in patients with inconclusive pre-surgery biopsy to tumor grades and aid in correct grade dependant surgical management of the lesion. Prediction of dedifferentiated chondrosarcoma from higher RAS will be attempted and a correlation to obtain a RAS cut off, although this may be challenging to achieve due to the overlap of features across the intermediate grade, high grade and dedifferentiated grades.

Radiology Aggressiveness correlates with the histologic grade in long bone extremity primary chondrosarcomas and the correlation of radiology and biopsy can aid in treatment planning by guiding us towards a low-grade neoplasm which may be dealt with intralesional extended curettage or high-grade lesion which need to be resected. Standalone RAS may not solve the grading dilemma of primary long bone intraosseous chondrosarcomas as the need for tissue diagnosis for confirming atypical cartilaginous neoplasm cannot be eliminated, however in the event of a needle biopsy grade or inconclusive open biopsy it may guide us towards a correlational diagnosis along with radiology and pathology for grade based management of the chondrosarcoma.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_13 | Pages 94 - 94
1 Dec 2022
Lazarides A Novak R Burke Z Gundavda M Ghert M Rose P Houdek M Wunder JS Ferguson P Griffin A Tsoi K
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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.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_13 | Pages 103 - 103
1 Dec 2022
Lazarides A Burke Z Gundavda M Griffin A Tsoi K Wunder JS Ferguson P
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Wide resection, with or without adjuvant therapy, is the mainstay of treatment for soft tissue sarcoma of the extremities. The surgical treatment of soft tissue sarcoma can portend a prolonged course of recovery from a functional perspective. However, data to inform the expected course of recovery following sarcoma surgery is lacking. The purpose of this study was to identify time to maximal functional improvement following sarcoma resection and to identify factors that delay the expected course of recovery.

A retrospective chart review was performed of all patients undergoing surgical treatment of a soft tissue sarcoma of the extremities between January 1st, 1985 and November 15, 2020 with a minimum of 1 follow up. The primary outcome measure was time to maximal functional improvement, defined as failure to demonstrate improvement on two consecutive follow up appointments, as defined by the functional outcome measures of Toronto Extremity Salvage Score (TESS) and Musculoskeletal Tumor Society (MSTS) Score or by achieving 90% of maximum outcome score.

We identified 1188 patients who underwent surgical resection of a soft tissue sarcoma of the extremities. Patients typically achieved a return to their baseline level of function by 1 year and achieved “maximal” functional recovery by 2 year's time postoperatively.

Patient and tumor factors that were associated with worse functional outcome scores and a delayed return to maximal functional improvement included older age (p=0.007), female sex (p-0.004), larger tumor size (p < 0 .001), deep tumor location (p < 0 .001), pelvic location (p < 0 .001), higher tumor grade (p < 0 .001). Treatment factors that were associated with worse functional outcome scores and a delayed return to maximal functional improvement included use of radiation therapy (p < 0 .001), perioperative complications (p < 0 .001), positive margin status (p < 0 .001) and return of disease, locally or systemically (p < 0 .001).

Most patients will recover their baseline function by 1 year and achieve “maximal” recovery by 2 years’ time following surgical resection for soft tissue sarcoma of the extremities. Several patient, tumor and treatment factors should be used to counsel patients as to a delayed course of recovery.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_13 | Pages 97 - 97
1 Dec 2022
Burke Z Lazarides A Gundavda M Griffin A Tsoi K Ferguson P Wunder JS
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Traditional staging systems for high grade osteosarcoma (Enneking, MSTS) are based largely on gross surgical margins and were developed before the widespread use of neoadjuvant chemotherapy. It is now well known that both microscopic margins and chemotherapy are predictors of local recurrence. However, neither of these variables are used in the traditional surgical staging and the precise safe margin distance is debated. Recently, a novel staging system utilizing a 2mm margin cutoff and incorporating precent necrosis was proposed and demonstrated improved prognostic value for local recurrence free survival (LRFS) when compared to the MSTS staging system. This staging system has not been validated beyond the original patient cohort. We propose to analyze this staging system in a cohort of patients with high-grade osteosarcoma, as well as evaluate the ability of additional variables to predict the risk of local recurrence and overall survival.

A retrospective review of a prospectively collected database of all sarcoma patients between 1985 and 2020 at a tertiary sarcoma care center was performed. All patients with high-grade osteosarcoma receiving neo-adjuvant chemotherapy and with no evidence of metastatic disease on presentation were isolated and analyzed. A minimum of two year follow up was used for surviving patients. A total of 225 patients were identified meeting these criteria. Univariate analysis was performed to evaluate variable that were associated with LRFS. Multivariate analysis is used to further analyze factors associated with LRFS on univariate analysis.

There were 20 patients (8.9%) who had locally recurrent disease. Five-year LRFS was significantly different for patients with surgical margins 2mm or less (77.6% v. 93.3%; p=0.006) and those with a central tumor location (67.9 v. 94.4; <0.001). A four-tiered staging system using 2mm surgical margins and a percent necrosis of 90% of greater was also a significant predictor of 5-year LRFS (p=0.019) in this cohort. Notably, percent necrosis in isolation was not a predictor of LRFS in this cohort (p=0.875). Tumor size, gender, and type of surgery (amputation v. limb salvage) were also analyzed and not associated with LRFS. The MSTS surgical margin staging system did not significantly stratify groups (0.066).

A 2mm surgical margin cutoff was predictive of 5-year LRFS in this cohort of patients with localized high-grade osteosarcoma and a combination of a 2mm margin and percent necrosis outperformed the prognostic value of the traditional MSTS staging system. Utilization of this system may improve the ability of surgeons to stage thier patients. Additional variables may increase the value of this system and further validation is required.


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_8 | Pages 38 - 38
1 Aug 2020
Mattei J Alshaygy I Basile G Griffin A Wunder JS Ferguson P
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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.


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_8 | Pages 4 - 4
1 Aug 2020
Basile G Alshaygy I Mattei J Griffin A Ferguson P Wunder JS
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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.


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_8 | Pages 5 - 5
1 Aug 2020
Alshaygy I Mattei J Basile G Griffin A Ferguson P Wunder JS
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Dermatofibrosarcoma protuberans (DFSP) is a rare, monoclonal dermal neoplasm. DFSP is known to be locally aggressive and infiltrative, but with a very low systemic recurrence risk. It is reported to be associated with high local recurrence rates following surgical excision. Positive or marginal resection margins can lead to a high risk of local recurrence. The objective was to determine the oncologic outcome for DFSP treated at our institution.

We reviewed our prospectively collected database for all DFSP treated at our unit between 1990 and 2016. Patients were included whether or not they had excision prior to referral (“whoops” procedure). Those with fibrosarcomatous degeneration at presentation to our unit or less than 1 year of follow-up were excluded. The goal of surgery was a negative margin with a minimum margin of 2 cm where possible. Patients were followed up after surgery to monitor complications, recurrence, transformation and/or metastasis.

139 patients with a mean age of 42.7 (SD=14.1) were included. Mean follow-up was 56 months.101 patients had prior “whoops” surgery before referral. 14 patients were also treated with radiotherapy (13 preoperatively, 1 postoperatively). Following surgery, 6 patients had positive margins, 4 underwent radiation treatment while the other 2 had no further treatment. One patient who presented to our unit with a local recurrence developed a further local recurrence, which demonstrated fibrosarcomatous degeneration at the time of resection (1/139, 0.7%). 1 other patient developed a lesion at another site.

The recurrence rate in our DFSP cohort is significantly lower than previous reports. Wide margin resection following oncologic principles can result in a very low recurrence rate. After the initial recovery phase, these patients do not require ongoing, frequent follow-up. Future studies should look at if closer margins can also produce similar treatment outcome.


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.