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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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.
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ItemOutcomes of unplanned sarcoma excision: impact of residual disease(WILEY, 2016-06)This study aimed to compare the oncological results between unplanned excision (UE) and planned excision (PE) of malignant soft tissue tumor and to examine the impact of residual tumor (ReT) after UE. Nonmetastatic soft tissue sarcomas surgically treated in 1996-2012 were included in this study. Disease-specific survival (DSS), metastasis-free survival (MFS), and local-recurrence-free survival (LRFS) were stratified according to the tumor location and American Joint Committee on Cancer Classification 7th edition stage. Independent prognostic parameters were identified by Cox proportional hazard models. Two-hundred and ninety PEs and 161 UEs were identified. Significant difference in oncological outcome was observed only for LRFS probability of retroperitoneal sarcomas (5-year LRFS: 33.0% [UE] vs. 71.0% [PE], P = 0.018). Among the 142 UEs of extremity and trunk, ReT in re-excision specimen were found in 75 cases (53%). UEs with ReT had significantly lower survival probabilities and a higher amputation rate than UEs without ReT (5-year DSS: 68.8% vs. 92%, P < 0.001; MFS: 56.1% vs. 90.9%, P < 0.001; LRFS: 75.8% vs. 98.4%, P = <0.001; amputation rate 18.5% vs. 1.8%, P = 0.003). The presence of ReT was an independent poor prognostic predictor for DSS, MFS, and LRFS with hazard ratios of 2.02 (95% confidence interval (CI), 1.25-3.26), 1.62 (95% CI, 1.05-2.51) and 1.94 (95% CI, 1.05-3.59), respectively. Soft tissue sarcomas should be treated in specialized centers and UE should be avoided because of its detrimental effect especially when ReT remains after UE.