Surgery (St Vincent's) - Research Publications
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ItemImportance of preoperative diagnosis for management of patients with suspected retroperitoneal sarcoma(WILEY, 2018-04)Soft tissue sarcoma is an umbrella term which encompasses over 60 histological tumour types. Approximately 15% of soft tissue sarcomas arise in the retroperitoneum. This complex group of tumours poses unique management challenges due to their often large size, histological heterogeneity and complexity of anatomical relationships. This review discusses the management of retroperitoneal tumours including the need for preoperative diagnosis, the evidence for neoadjuvant radiotherapy, the role of multivisceral resection and the importance of a multidisciplinary team approach.
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ItemDiagnostic accuracy of computed tomography-guided biopsy in pathological fractures(WILEY, 2017-07)BACKGROUND: Obtaining a histological diagnosis is essential for appropriate management of pathological fractures. Computed tomography (CT) is an accurate method of obtaining diagnosis for musculoskeletal tumours. We analysed whether diagnostic accuracy was maintained in the evaluation of pathological fractures. METHODS: A retrospective review of 101 consecutive patients presenting to our tertiary musculoskeletal tumour centre with pathological fracture was performed. Patients underwent core needle biopsy under CT guidance of pathological fractures diagnosed by plain radiography and either CT or magnetic resonance imaging. The histopathology of the CT-guided biopsy was compared with the sample obtained from open biopsy or definitive surgery to determine diagnostic accuracy. RESULTS: The mean age at diagnosis was 52 ± 20 years (range: 18-85) in a cohort of 46 men and 55 women. Diagnostic accuracy of CT-guided biopsy was 82.18%. There were 65 malignant and 36 benign tumours with diagnostic accuracy of 86.15% and 80.56%, respectively. The positive predictive value for a malignant tumour was 98.21% whilst it was 93.1% for benign tumours. The femur (53 cases) and humerus (25 cases) were the commonest bones fractured. The most frequent diagnoses were metastasis (20.79%), giant cell tumour (17.82%), osteosarcoma (9.90%) and myeloma (9.90%). There were no complications of CT-guided biopsy. CONCLUSION: Pathological fracture does not confound the diagnosis of musculoskeletal tumours. CT-guided biopsy is an accurate diagnostic tool in the evaluation of pathological fractures. Final diagnosis and management should be made in the context of appropriate anatomical and functional imaging using a multidisciplinary approach.
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ItemPredicting the prognosis of undifferentiated pleomorphic soft tissue sarcoma: a 20-year experience of 266 cases(WILEY, 2019-09)BACKGROUND: Undifferentiated pleomorphic sarcoma (UPS) is a rare malignant tumour of mesenchymal origin, which was conceived following re-classification of malignant fibrous histiocytoma (MFH). The objective of this study is to determine prognostic factors for the outcome of UPS, following multi-modal treatment. METHODS: Data of UPS tumours from 1996 to 2016 were collected, totalling 266 unique UPS patients. Median follow-up was 7.8 years. All tumours were retrospectively analysed for prognostic factors of the disease, including local recurrence (LR) and metastatic disease (MD) at diagnosis, tumour size, grade, location and depth, patient age, adjuvant therapy and surgical margin. Overall survival (OS), post-treatment LR and metastatic-free survival were assessed as outcomes. RESULTS: The 5- and 10-year OS rates for all ages were 60% and 48%, respectively, with a median survival time of 10.1 years. Multivariate analysis revealed that the adverse prognostic factors associated with decreased OS were older age (P < 0.001; hazard ratio 1.03) and MD at diagnosis (P = 0.001; 2.89), with upper extremity tumours being favourable (P = 0.043; 2.30). Poor prognosis for post-operative LR was associated with older age (P = 0.046; 1.03) and positive surgical margins (P = 0.028; 2.68). Increased post-treatment MD was seen in patients with large tumours (5-9 cm (P < 0.001; 4.42), ≥10 cm (P < 0.001; 6.80)) and MD at diagnosis (P < 0.001; 3.99), adjuvant therapy was favourable, shown to reduce MD (P < 0.001; 0.34). CONCLUSIONS: UPS is a high-grade soft tissue sarcoma, for which surgery striving for negative margins, with radiotherapy, is the treatment of choice. Older age, lower extremity location, MD at presentation, large size and positive surgical margins, were unfavourable.
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ItemDual-energy contrast-enhanced CT to evaluate scaphoid osteonecrosis with surgical correlation(WILEY, 2019-02)To evaluate the validity of contrast enhanced dual energy CT using a lung perfusion algorithm in assessing for post-traumatic scaphoid proximal pole avascular necrosis. From Aug 2013 to Aug 2016, 18 patients (19 wrists, 16 males, 2 females, mean age 28 years) were assessed as high-risk for proximal pole scaphoid avascular necrosis by a single surgeon following a scaphoid fracture and were referred for contrast-enhanced dual energy CT. 8 wrists had specimens sent for correlative histological analysis and 11 were correlated with operative notes. Eight surgical specimens were sent to histology and showed a 100% correlation (8/8) with the DECT findings. The remaining 11 wrists that did not have a specimen sent had in-surgery findings that also correlated with DECT. A single case was discrepant (1/11) due to presence of an intra-osseous ganglion, which was reported as osteonecrosis on CT, but considered viable at surgery. No case was called viable on CT that proved to be necrotic at either surgery or histologically. Contrast-enhanced dual energy CT using a perfusion algorithm is an innovative and promising method in evaluating viability of the post-trauma proximal pole of scaphoid.
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ItemClinical, radiological and pathological outcomes following treatment of primary giant cell tumour of bone with Denosumab(WILEY, 2020-12)BACKGROUND: Giant cell tumour of bone (GCTOB) is a relatively uncommon, benign, but locally aggressive neoplasm. Denosumab is a fully human monoclonal antibody with inhibitory effects on receptor activator of nuclear factor kappa-B ligand that has shown early promise as a possible treatment adjuvant for GCTB. However, much is still unknown about its current indications, long-term effects, the potential risk for rapid relapse and its involvement in sarcomatous transformation. METHODS: We analysed the outcomes of 154 patients with GCTOB. We assessed clinical outcomes via local recurrence free-survival, metastatic free-survival and sarcomatous transformation between those treated without Denosumab and those with neo-adjuvant Denosumab. Our radiological and pathological outcomes were assessed through independent specialist reviews. RESULTS: Four (19.0%) patients of the neo-adjuvant group had local recurrence of disease versus 16 (12.0%) patients in the surgery alone group; this results in a 3.62 times increased likelihood of developing local recurrence (P = 0.030). The median time to local recurrence was shorter for the neo-adjuvant group (421.5 days versus 788.5 days) (P = 0.01). There was no difference between Denosumab and the surgery groups in terms of metastatic disease (P = 0.45). Two patients in our cohort with GCTOB developed sarcomatous transformation, both were treated with Denosumab. CONCLUSION: Our use of Denosumab tended to be for those patients who had surgically difficult tumours to halt the progression and allow easier resections. Of concern we noted a trend towards increasing recurrence rates with the potential risk for rapid relapse. Furthermore, two cases experienced sarcomatous transformation, which is a growing area of concern within the literature.
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ItemCutaneous leiomyosarcoma: dermal and subcutaneous(WILEY, 2020-08)BACKGROUND AND OBJECTIVES: Leiomyosarcoma of skin (LMS) can be sub-classified on pathology appearances as Dermal or Subcutaneous. The aim of this study was to provide treatment recommendations for these uncommon tumours. METHODS: A retrospective review of all patients with dermal and subcutaneous leiomyosarcoma managed at the Peter MacCallum Cancer Centre, Australia from January 2003 to December 2018 was performed. Eighty-three patients were identified (64 dermal leiomyosarcoma, 19 subcutaneous leiomyosarcoma). RESULTS: Subcutaneous leiomyosarcoma were larger (median size 14 mm dermal, 49 mm subcutaneous, P = 0.01). No patient with a dermal leiomyosarcoma developed metastatic disease compared to 4 of the 19 subcutaneous leiomyosarcoma (5-year overall survivals, 98% and 88%, respectively, P = 0.03). The most common site of metastasis was to the lung. No difference in risk of local recurrence was apparent (5-year recurrence-free survivals were 85% and 78%, respectively, P = 0.17). Adjuvant radiotherapy was used in 16 (25%) dermal leiomyosarcoma patients and 13 (68%) subcutaneous leiomyosarcoma patients (P < 0.001). Local recurrence was uncommon in both tumour subtypes when patients received definitive surgical excision (minimum histological margins of 10 mm as per institutional protocol) regardless of whether radiotherapy was used. The 5-year local recurrence-free survival for dermal leiomyosarcoma treated with radiotherapy was 93% versus 83% without radiotherapy (P = 0.7) and for subcutaneous leiomyosarcoma was 69% and 100%, respectively (P = 0.9). CONCLUSIONS: Dermal leiomyosarcoma have an excellent prognosis, particularly after definitive surgical excision with margins of at least 10 mm. Subcutaneous leiomyosarcoma has poorer outcomes and should be managed by wider excision and considered for adjuvant radiotherapy.
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ItemCorrelation between percutaneous biopsy and final histopathology for retroperitoneal sarcoma: a single-centre study(WILEY, 2020-04)BACKGROUND: Retroperitoneal sarcomas are rare soft tissue tumours accounting for 10-15% of soft tissue sarcomas. Patient prognosis and treatment recommendations (including extent of surgery and neoadjuvant strategies) are determined by the pre-operative histopathological subtype and grade obtained from biopsy and thus it is important to understand the accuracy of biopsy in retroperitoneal masses. METHODS: This study presents a case series of primary retroperitoneal sarcomas managed at Peter MacCallum Cancer Centre (PMCC) between 2008 and 2019. Statistical analyses were performed to determine correlation between histopathology from percutaneous biopsy and surgical excision. RESULTS: A total of 117 patients who underwent percutaneous core biopsy and surgical excision of retroperitoneal sarcoma were included. Diagnostic accuracy varied with histopathological diagnosis, but overall precise concordance between biopsy and final histopathology was seen in 61% (κ = 0.57). Biopsy was most sensitive for identifying well-differentiated liposarcoma (WDLPS) (sensitivity 85%, 95% CI 0.06-0.96) and leiomyosarcoma (sensitivity 81%, 95% CI 0.54-0.96) and was least sensitive for identifying de-differentiated liposarcoma (DDLPS) (sensitivity 40%, 95% CI 0.25-0.56). Overall agreement between biopsy and final histopathology increased with use of PET/CT scan pre-biopsy and with use of fluorescence in situ hybridisation testing on biopsy, however, neither test improved recognition of de-differentiated components within WD/DDLPS on core biopsy. CONCLUSIONS: Pre-operative biopsy is important for clinical decision making in the treatment of retroperitoneal sarcoma. A significant portion of patients with a WDLPS will have a de-differentiated component identified at the time of resection that was not identified on initial biopsy.
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ItemA phase Ib/II translational study of sunitinib with neoadjuvant radiotherapy in soft-tissue sarcoma(NATURE PUBLISHING GROUP, 2014-12-09)BACKGROUND: Preoperative radiotherapy (RT) is commonly used to treat localised soft-tissue sarcomas (STS). Hypoxia is an important determinant of radioresistance. Whether antiangiogenic therapy can 'normalise' tumour vasculature, thereby improving oxygenation, remains unknown. METHODS: Two cohorts were prospectively enrolled. Cohort A evaluated the implications of hypoxia in STS, using the hypoxic tracer (18)F-azomycin arabinoside (FAZA-PET). In cohort B, sunitinib was added to preoperative RT in a dose-finding phase 1b/2 design. RESULTS: In cohort A, 13 out of 23 tumours were hypoxic (FAZA-PET), correlating with metabolic activity (r(2)=0.85; P<0.001). Two-year progression-free (PFS) and overall (OS) survival were 61% (95% CI: 0.44-0.84) and 87% (95% CI: 0.74-1.00), respectively. Hypoxia was associated with radioresistance (P=0.012), higher local recurrence (Hazard ratio (HR): 10.2; P=0.02), PFS (HR: 8.4; P=0.02), and OS (HR: 41.4; P<0.04). In Cohort B, seven patients received sunitinib at dose level (DL): 0 (50 mg per day for 2 weeks before RT; 25 mg per day during RT) and two patients received DL: -1 (37.5 mg per day for entire period). Dose-limiting toxicities were observed in 4 out of 7 patients at DL 0 and 2 out of 2 patients at DL -1, resulting in premature study closure. Although there was no difference in PFS or OS, patients receiving sunitinib had higher local failure (HR: 8.1; P=0.004). CONCLUSION: In STS, hypoxia is associated with adverse outcomes. The combination of sunitinib with preoperative RT resulted in unacceptable toxicities, and higher local relapse rates.
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ItemAnti-osteoclastic agent, denosumab, for a giant cell tumor of the bone with concurrent Paget's disease: A case report(SPANDIDOS PUBL LTD, 2017-04)Paget's disease of the bone may predispose the development of malignant bone tumors such as osteosarcoma. Giant cell tumor (GCT) as a consequence of Paget's disease is rare. Bone GCT is characterized by rapid growth, the destruction of bone, extension to the surrounding soft tissue and abnormal bone turnover caused by an abnormality of the receptor activator of nuclear factor-κB (RANK)-RANK ligand (RANKL) pathway. Denosumab is a RANK-RANKL inhibitor, which is used to treat osteoporosis and bone GCT. In the current study, a 60-year-old male presented with severe pain located between the right thigh and the knee. The patient could not bear weight on the affected leg. The patient had suffered from Paget's disease for 15 years. The complications from Paget's disease included degenerative hip disease, for which the patient underwent a right total hip replacement. A right periacetabular lesion was identified and confirmed as Paget's disease-induced GCT by needle biopsy. A positron emission tomography (PET) scan revealed significant tumor metabolic activity. Subsequent to obtaining informed consent, the patient started treatment with denosumab. A total of 2.5 months after starting denosumab, a PET scan showed no residual pathological uptake at the site of the previously identified large PET avid tumor. After 1 year, the patient exhibited a satisfactory clinical improvement. In conclusion, treatment with denosumab markedly reduced the size of the hemi-pelvic GCT and led to a complete metabolic response.
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ItemClinical Features of High-Grade Extremity and Trunk Sarcomas in Patients Aged 80 Years and Older: Why Are Outcomes Inferior?(FRONTIERS MEDIA SA, 2019-05-31)Background: The population of many countries is aging and a significant number of elderly patients with soft-tissue sarcoma are being seen at cancer centers. The unique therapeutic and prognostic implications of treating soft-tissue sarcoma in geriatric patients warrant further consideration in order to optimize outcomes. Patients and Methods: This is a single-institution retrospective study of consecutive non-metastatic primary extremity and trunk high-grade sarcomas surgically treated between 1996 and 2012, with at least 2 years of follow-up for survivors. Patient characteristics and oncological outcomes were compared between age groups (≥80 vs. <80 years), using Chi-square or Fisher-exact test and Log-Rank or Wilcoxon test, respectively. Deaths from other causes were censored for disease-specific survival estimation. A p< 0.05 was regarded as statistically significant. Results: A total of 333 cases were eligible for this study. Thirty-six patients (11%) were aged ≥80 years. Unplanned surgery incidence and surgical margin status were comparable between the age groups. Five-year local-recurrence-free, metastasis-free and disease-specific survivals were 72% (≥80 years) vs. 90% (<80 years) (p = 0.004), 59 vs. 70% (p = 0.07) and 55 vs. 80% (p < 0.001), respectively. A significantly earlier first metastasis after surgery (8.3 months vs. 20.5 months, mean) and poorer survival after first metastasis (p = 0.03) were observed. Cox analysis revealed "age ≥80 years" as an independent risk factor for local failure and disease-specific mortality, with hazard ratios of 2.41 (95% CI: 1.09-5.32) and 2.52 (1.33-4.13), respectively. A competing risks analysis also showed that "age ≥80 years" was significantly associated with the disease-specific mortality. Conclusions: Oncological outcomes were significantly worse in high-grade sarcoma patients aged ≥80 years. The findings of more frequent local failure regardless of a consistent primary treatment strategy, an earlier time to first metastasis after surgery, and poorer prognosis after first metastasis suggest that more aggressive tumor biology, in addition to multiple co-morbidity, may explain the inferiority.