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    A pilot study investigating the role of 18F-FDG-PET in the early identification of chemoradiotherapy response in anal cancer
    Smith, D ; Joon, DL ; Knight, K ; Sim, J ; Schneider, M ; Lau, E ; Foroudi, F ; Khoo, V (WILEY, 2022-12)
    INTRODUCTION: Anal cancer (AC) is 18 F-FDG-PET avid and has been used to evaluate treatment response several months after chemoradiotherapy. This pilot study aimed to assess the utility of semi-automated contouring methods and quantitative measures of treatment response using 18 F-FDG-PET imaging at the early time point of 1-month post-chemoradiotherapy. METHODS: Eleven patients with AC referred for chemoradiotherapy were prospectively enrolled into this study, with 10 meeting eligibility requirements. 18 F-FDG-PET imaging was obtained pre-chemoradiotherapy (TP1), and then 1-month (TP2), 3-6 months (TP3) and 9-12 months (TP4) post-chemoradiotherapy. Manual and semi-automated (Threshold) contouring methods were used to define the primary tumour on all 18 F-FDG-PET images. Resultant contours from each method were interrogated using quantitative measures, including volume, response index (RI), total lesion glycolysis (TLG), SUVmax , SUVmedian and SUVmean . Response was assessed quantitatively as reductions in these measures and also qualitatively against established criteria. RESULTS: Nine patients were qualitatively classified as complete metabolic responders at TP2 and all 10 at TP3. All quantitative measures demonstrated significant (P < 0.05) reductions at TP2 for both Manual and Threshold methods. All reduced further at TP3 and again at TP4 for Threshold methods. TLG showed the highest reduction at all post-chemoradiotherapy time points and classified the most responders for each method at each time point. All patients are recurrence-free at minimum 4-year follow-up. CONCLUSION: Based on our small sample size, semi-automated methods of disease definition using 18 F-FDG-PET imaging are feasible and appear to facilitate quantitative response classification of AC as early as 1-month post-chemoradiotherapy. Early identification of treatment response may potentially improve disease management.
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    Defining primary anal cancer tumour volume on FDG–PET – an initial assessment of semi–automated methods
    Smith, D ; Joon, DL ; Schneider, M ; Lau, E ; Knight, K ; Foroudi, F ; Khoo, V (MedCrave Group, LLC, 2021-01-12)
    Purpose Clinician inexperience, intra–observer and inter–observer variations in tumour definition may affect staging, radiotherapy target definition, and treatment outcomes, particularly in rare cancers. The purpose of this study was to assess the correlation between semi–automated methods of primary anal cancer (AC) definition and our current clinical standard of manual clinician definition using 18F–FDG–PET imaging and to provide recommendations for clinical use. Methods All patients referred for chemoradiotherapy for AC between 2012 and 2016 were prospectively enrolled, with all 18F–FDG–PET imaging acquired within one year of chemoradiotherapy collected. Three methods of primary AC definition were performed on all PET datasets. Manual definition by an experienced radiologist was considered the clinical standard for comparison of volume and coincidence (Dice coefficient) in our study. Semi–automated techniques assessed included a gradient–based SUV (SUV–gradient) method and a SUV threshold method with a range of thresholds relative to SUVmax (40 (T40), 50 (T50) and 60% (T60)). Results Ten patients were enrolled with 33 PET study sets available for analysis. While all methods created contours on pre– and post–treatment scans, manual definition of PET–avid disease was only necessary on 11 of the 33 study sets. SUV–gradient and T40 defined contours were not statistically different in volume to the clinical standard (p = 0.83 & 0.72 respectively). The observed Dice coefficient relative to the manual clinician contours were 0.75 and 0.73 for the SUV–gradient and T40 methods respectively. Conclusions It is possible to define gross AC using SUV–based methods, with the SUV–gradient–based method followed by the T40 method most closely correlating with our current clinical standard. The SUV–gradient–based method studied is housed within a proprietary clinical system. A semi–automated approach that uses a vendor neutral T40 method and the clinician’s knowledge and skill appears optimal in defining AC. With this approach AC may be defined reliably to enhance efficiencies in radiotherapy and nuclear medicine processes, and to support clinicians in identifying and defining this rare disease. Trial registration ANZCTR, ACTRN12620000066987. Registered 28 January 2020–Retrospectively registered, https://www.anzctr.org.au/ACTRN12620000066987.aspx
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    Prostate-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
    Ong, WL ; Koh, TL ; Joon, DL ; Chao, M ; Farrugia, B ; Lau, E ; Khoo, V ; Lawrentschuk, N ; Bolton, D ; Foroudi, F (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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    TROG 15.03 phase II clinical trial of Focal Ablative STereotactic Radiosurgery for Cancers of the Kidney - FASTRACK II
    Siva, S ; Chesson, B ; Bressel, M ; Pryor, D ; Higgs, B ; Reynolds, HM ; Hardcastle, N ; Montgomery, R ; Vanneste, B ; Khoo, V ; Ruben, J ; Lau, E ; Hofman, MS ; Lourenco, RDA ; Sridharan, S ; Brook, NR ; Martin, J ; Lawrentschuk, N ; Kron, T ; Foroudi, F (BMC, 2018-10-23)
    BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is a non-invasive alternative to surgery to control primary renal cell cancer (RCC) in patients that are medically inoperable or at high-risk of post-surgical dialysis. The objective of the FASTRACK II clinical trial is to investigate the efficacy of SABR for primary RCC. METHODS: FASTRACK II is a single arm, multi-institutional phase II study. Seventy patients will be recruited over 3 years and followed for a total of 5 years. Eligible patients must have a biopsy confirmed diagnosis of primary RCC with a single lesion within a kidney, have ECOG performance ≤2 and be medically inoperable, high risk or decline surgery. Radiotherapy treatment planning is undertaken using four dimensional CT scanning to incorporate the impact of respiratory motion. Treatment must be delivered using a conformal or intensity modulated technique including IMRT, VMAT, Cyberknife or Tomotherapy. The trial includes two alternate fractionation schedules based on tumour size: for tumours ≤4 cm in maximum diameter a single fraction of 26Gy is delivered; and for tumours > 4 cm in maximum diameter 42Gy in three fractions is delivered. The primary outcome of the study is to estimate the efficacy of SABR for primary RCC. Secondary objectives include estimating tolerability, characterising overall survival and cancer specific survival, estimating the distant failure rate, describing toxicity and renal function changes after SABR, and assessment of cost-effectiveness of SABR compared with current therapies. DISCUSSION: The present study design allows for multicentre prospective validation of the efficacy of SABR for primary RCC that has been observed from prior single institutional and retrospective series. The study also allows assessment of treatment related toxicity, overall survival, cancer specific survival, freedom from distant failure and renal function post therapy. TRIAL REGISTRATION: Clinicaltrials.gov NCT02613819 , registered Nov 25th 2015.