Surgery (Austin & Northern Health) - Research Publications
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ItemEffects of aromatase inhibitor therapy on visceral adipose tissue area and cardiometabolic health in postmenopausal women with early and locally advanced breast cancer(WILEY, 2023-02)OBJECTIVE: Aromatase inhibitor (AI) therapy provides oncological benefits in postmenopausal women with oestrogen receptor-positive breast cancer. However, AI treatment has been associated with increased cardiovascular risk. In nonbreast cancer populations, experimentally induced low oestrogen states and natural transition to menopause have been associated with increases in visceral adipose tissue (VAT), a known surrogate marker for cardiometabolic risk. Given that AI treatment blocks oestradiol production, we hypothesized that AI treatment would increase VAT. METHODS: We conducted a prospective 12-month cohort study of 52 postmenopausal women newly initiating AI treatment (median age: 64.5 years) and 52 women with breast pathology not requiring endocrine therapy (median age: 63.5 years). VAT area and other body composition parameters were measured at baseline, 6 months and 12 months using dual X-ray absorptiometry. Other risk markers of cardiometabolic health were also assessed. RESULTS: In women initiating AI treatment, there was no statistically significant difference in VAT area after 12 months when compared to controls, with a mean adjusted difference of -5.00 cm2 (-16.9, 6.91), p = .55. Moreover, changes in total fat mass, lean mass, subcutaneous adipose tissue area, hepatic steatosis and measures in endothelial function were also not statistically different between groups after 12 months. Findings were similar after adjustments for activity levels and coronavirus disease 2019 lockdown duration. CONCLUSIONS: These data provide reassurance that over the initial 12 months of AI therapy, AI treatment is not associated with metabolically adverse changes in body composition, hepatic steatosis or vascular reactivity. The impact of extended AI therapy on cardiometabolic health requires further study.
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ItemComprehensive review of the use of hydrogel spacers prior to radiation therapy for prostate cancer(WILEY, 2023-03)OBJECTIVES: To provide a comprehensive narrative review of the published data on the impact of hydrogel spacers on rectal dosimetry and toxicity and to outline the practicalities of inserting hydrogel spacers. RESULTS: A growing body of evidence suggests that the administration of hydrogel spacers is safe and is associated with limited peri-operative morbidity. The impact on rectal dosimetry has been clearly established and use of hydrogel spacers is associated with reduced rectal morbidity. These results have been corroborated by several Phase II and III clinical trials and subsequent meta-analysis. There are several areas for future research, including the role of hydrogel spacers in prostate stereotactic beam radiotherapy and post-radiotherapy local recurrence. CONCLUSIONS: Hydrogel spacers provide a low-morbidity method to potential reduce rectal toxicity after radiation therapy in men with prostate cancer. Data outlining sexual function and oncological outcomes are limited to date. Future studies, currently being conducted, may provide further clarification of the role of hydrogel spacers in prostate cancer management.
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ItemA clinical study comparing polymer and gold fiducials for prostate cancer radiotherapy.(Frontiers Media SA, 2022)INTRODUCTION: Image guidance with gold fiducials improves outcomes of prostate radiotherapy. However, gold produces artefact on CT imaging, interfering with contouring and verification. The purpose of this study was to compare polymer to standard gold fiducials using radiotherapy imaging modalities to assess the visibility and artefact. METHODS: Twenty eight patients with locally advanced prostate cancer were enrolled, half had three polymer fiducials implanted into the prostate and half underwent insertion of gold fiducials. Patients were imaged with CT, T2 weighted MRI, cone-beam CT (CBCT) and planar KV images. Fiducials were scored for visibility and assessed for CT artefact in surrounding prostate tissue. The artefact was quantified from Hounsfield number histograms and separated into percentile ranges and proportion of voxels in HU normal tissue range of a 2cm sphere surrounding the fiducial. RESULTS: Gold and polymer fiducials were sufficiently visible for CT and CBCT verification. The gold fiducials could be visualized well on KV planar imaging; however, the polymer markers were obscured by pelvic bones. Neither polymer nor gold fiducials could be visualized on MRI. The polymer fiducial produced less artefact than gold on CT, having less voxel spread for the HU percentile ranges and a greater proportion of voxels in the normal tissue range. CONCLUSIONS: Polymer fiducials are a more suitable fiducial than gold for CT/CBCT in prostate cancer radiotherapy, demonstrating minimal artefact and good visibility on CT. However, they were not well seen on MRI or KV imaging and thus not suitable for co-registration or planar KV verification.
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ItemChoosing Wisely in radiation therapy for breast cancer: Time lag in adoption of hypofractionated radiation therapy in Victoria(WILEY, 2021-04)INTRODUCTION: To evaluate the adoption of hypofractionated radiotherapy (HFRT) for breast cancer (BC) in Victoria, Australia. METHODS: This is a population-based cohort of women with BC who had breast RT as captured in the Victorian Radiotherapy Minimum Data Set between 2012 and 2017. We defined HFRT as < 25 fractions of RT. The pattern of HFRT use over time was evaluated with the Cochrane-Armitage test for trend. Factors associated with HFRT were identified using multivariable logistic regression. RESULTS: 12,717 women were included in the study. Overall, 6,653 (52%) patients had HFRT. HFRT use increased from 35% in 2012 to 66% in 2017 (P-trend < 0.001). Older women were more likely to have HFRT (74% for women aged ≥ 70 years vs. 27% for women aged < 50 years; P < 0.001). Women who had nodal irradiation were less likely to have HFRT compared with those who did not (13% vs. 57%; P < 0.001). HFRT use was more common in public than private institutions (57% vs. 46%, P < 0.001), and in metropolitan than regional centres (54% vs. 46%, P < 0.001). In multivariable analyses, the progressive increase in HFRT use over time was independent of other covariates - women treated in 2017 were 7.3 times (95% CI = 6.3-8.6, P < 0.001) more likely to be treated with HFRT than in 2012. Age at RT, nodal irradiation, area of residence and institutional type and locations were all independently associated with HFRT use. CONCLUSION: This large Australian contemporary population-based study demonstrates increasing use of HFRT for BC. However, large sociodemographic and institutional provider-related variations in practice still exist.
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ItemProstate-specific membrane antigen-positron emission tomography/computed tomography (PSMA-PET/CT)-guided stereotactic ablative body radiotherapy for oligometastatic prostate cancer: a single-institution experience and review of the published literature(WILEY, 2019-11)OBJECTIVES: To report the outcomes of stereotactic ablative body radiotherapy (SABR) in men with oligometastatic prostate cancer (PCa) diagnosed on prostate-specific membrane antigen (PSMA)-positron emission tomography/computed tomography (PET/CT), based on a single-institution experience and the published literature. PATIENTS AND METHODS: This was a retrospective cohort study of the first 20 consecutive men with oligometastatic PCa, treated with SABR in a single institution, who had biochemical recurrence after previous curative treatment (surgery/radiotherapy), had no evidence of local recurrence, were not on palliative androgen deprivation therapy (ADT), and had PSMA-PET/CT-confirmed oligometastatic disease (≤3 lesions). These men were treated with SABR to a dose of 30 Gy in three fractions for bone metastases, and 35-40 Gy in five fractions for nodal metastases. The outcomes of interest were: PSA response; local progression-free survival (LPFS); distant progression-free survival (DPFS); and ADT-free survival (ADTFS). A literature review was performed to identify published studies reporting on outcomes of PSMA-PET/CT-guided SABR. RESULTS: In our institutional cohort, 12 men (60%) had a decline in PSA post-SABR. One man had local progression 9.6 months post-SABR, with 12-month LPFS of 93%. Ten men had distant progression outside of their SABR treatment field, confirmed on PSMA-PET/CT, with 12-month DPFS of 62%, of whom four were treated with palliative ADT, two received prostate bed radiotherapy for prostate bed progression (confirmed on magnetic resonance imaging), and four received a further course of SABR (of whom one had further progression and was treated with palliative ADT). At last follow-up, six men (one with local progression and five with distant progression) had received palliative ADT. The 12-month ADTFS was 70%. Men with longer intervals between local curative treatment and SABR had better DPFS (P = 0.03) and ADTFS (P = 0.005). Four additional studies reporting on PSMA-PET/CT-guided SABR for oligometastatic PCa were identified and included in the review, giving a total of 346 patients. PSA decline was reported in 60-70% of men post-SABR. The 2-year LPFS, DPFS and ADTFS rates were 76-100%, 27-52%, and 58-62%, respectively. CONCLUSION: Our results showed that PSMA-PET/CT could have an important role in identifying men with true oligometastatic PCa who would benefit the most from metastases-directed therapy with SABR.
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ItemHigh dose rate brachytherapy boost for prostate cancer: Biochemical control and the impact of transurethral resection of the prostate and hydrogel spacer insertion on toxicity outcomes(WILEY, 2019-06)INTRODUCTION: To examine the long-term outcomes of high dose rate brachytherapy boost (HDR-BT) combined with external beam radiotherapy (EBRT) for intermediate and high-risk prostate cancer patients. METHODS: Data from 95 patients who underwent combined EBRT (50.4 Gy) and HDR-BT to the prostate between 2010 and 2017 were retrospectively analysed. Biochemical progression free survival (bPFS), local recurrence free survival (LRFS), metastatic free survival (MFS) and overall survival (OS) were estimated using Kaplan-Meier method. Regression analysis was conducted to identify important predictors of outcomes. RESULTS: A total of 24 patients received an initial HDR-BT dose of 18 Gy in three fractions, with the remaining 71 patients receiving 16 Gy in two fractions as per departmental protocol changes. Most patients (88%) received androgen deprivation therapy. A transurethral resection of the prostate (TURP) was performed in 14 patients and hydrogel spacers (HS) were used in 30 patients. Median follow-up was 58 months. The 5-year bPFS, LRFS, MFS and OS were 92%, 100%, 92% and 88%. Univariate regression revealed no statistical association between patient characteristics and time to relapse (all P > 0.1). Late > grade 2 genitourinary (GU) toxicity was 6.3%. The use of HS or prior TURP had no impact on late GU toxicity. Late Grade 1 gastrointestinal (GI) toxicity was 5.3%. CONCLUSION: The combined HDR-BT with EBRT resulted in excellent bPFS. The cumulative risk of late GU and GI toxicity was low and can be further improved with preventative strategies such as a pre-emptive TURP and/or HS insertion.
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ItemProspective analysis of hydrogel spacer for patients with prostate cancer undergoing radiotherapy(WILEY, 2018-09)OBJECTIVE: To report on the dosimetric benefits and late toxicity outcomes after injection of hydrogel spacer (HS) between the prostate and rectum for patients treated with prostate radiotherapy (RT). PATIENTS AND METHODS: In all, 76 patients with a clinical stage of T1-T3a prostate cancer underwent general anaesthesia for fiducial marker insertion plus injection of the HS into the perirectal space before intensity-modulated RT (IMRT) or volumetric-modulated arc RT (VMAT). HS safety, dosimetric benefits, and the immediate- to long-term effects of gastrointestinal (GI) toxicity were assessed. RESULTS: There were no postoperative complications reported. The mean (range) prostate size was 66.0 (25.0-187.0) mm. Rectal dose volume parameters were observed and the volume of rectum receiving 70 Gy (rV70 ), 75 Gy (rV75 ) and 78 Gy (rV78 ) was 7.8%, 3.6% and 0.4%, respectively. In all, 21% of patients (16/76) developed acute Grade 1 GI toxicities, but all were resolved completely by 3 months after treatment; whilst, 3% of patients (2/76) developed late Grade 1 GI toxicities. No patients had acute or late Grade ≥2 GI toxicities. CONCLUSION: Injection of HS resulted in a reduction of irradiated rectal dose volumes along with minimal GI toxicities, irrespective of prostate size.
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ItemVertebral fractures following stereotactic body radiotherapy for spine metastases(WILEY, 2020-04)Stereotactic body radiotherapy has emerged as one of the preferred treatments for patients with spine metastases, with the potential for long-term control from lesion irradiation. Post-treatment vertebral compression fractures are a known complication of this therapy, contributing to worsening pain and reduced quality of life, sometimes requiring surgical intervention. This review explores the current knowledge of post-radiotherapy fractures, in terms of the rates and associated predictive factors. A search of databases including Medline, Embase and the Cochrane Library was conducted using keywords such as 'vertebral compression fracture', 'stereotactic body radiotherapy' and 'spine metastases'. The search was limited to published studies up to March 2019, reporting clinical outcomes including both the post-treatment fracture rate and statistical identification of associated risk factors. Rates of post-treatment fractures ranged from 4 to 39%. A variety of factors were found to increase the risk, including the appearance of lytic vertebral disease, degree of pre-existing compression, spinal malalignment, increased dose per fraction and a Spinal Instability Neoplastic Score >6. This knowledge can enable clinicians to counsel patients when considering management options for spine metastases, maintaining the balance between local tumour control and the risk of subsequent fracture.