Sir Peter MacCallum Department of Oncology - Research Publications

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    Stereotactic ablative body radiotherapy for inoperable primary kidney cancer: a prospective clinical trial
    Siva, S ; Pham, D ; Kron, T ; Bressel, M ; Lam, J ; Tan, TH ; Chesson, B ; Shaw, M ; Chander, S ; Gill, S ; Brook, NR ; Lawrentschuk, N ; Murphy, DG ; Foroudi, F (WILEY, 2017-11)
    OBJECTIVE: To assess the feasibility and safety of stereotactic ablative body radiotherapy (SABR) for renal cell carcinoma (RCC) in patients unsuitable for surgery. Secondary objectives were to assess oncological and functional outcomes. MATERIALS AND METHODS: This was a prospective interventional clinical trial with institutional ethics board approval. Inoperable patients were enrolled, after multidisciplinary consensus, for intervention with informed consent. Tumour response was defined using Response Evaluation Criteria In Solid Tumors v1.1. Toxicities were recorded using Common Terminology Criteria for Adverse Events v4.0. Time-to-event outcomes were described using the Kaplan-Meier method, and associations of baseline variables with tumour shrinkage was assessed using linear regression. Patients received either single fraction of 26 Gy or three fractions of 14 Gy, dependent on tumour size. RESULTS: Of 37 patients (median age 78 years), 62% had T1b, 35% had T1a and 3% had T2a disease. One patient presented with bilateral primaries. Histology was confirmed in 92%. In total, 33 patients and 34 kidneys received all prescribed SABR fractions (89% feasibility). The median follow-up was 24 months. Treatment-related grade 1-2 toxicities occurred in 26 patients (78%) and grade 3 toxicity in one patient (3%). No grade 4-5 toxicities were recorded and six patients (18%) reported no toxicity. Freedom from local progression, distant progression and overall survival rates at 2 years were 100%, 89% and 92%, respectively. The mean baseline glomerular filtration rate was 55 mL/min, which decreased to 44 mL/min at 1 and 2 years (P < 0.001). Neutrophil:lymphocyte ratio correlated to % change in tumour size at 1 year, r2 = 0.45 (P < 0.001). CONCLUSION: The study results show that SABR for primary RCC was feasible and well tolerated. We observed encouraging cancer control, functional preservation and early survival outcomes in an inoperable cohort. Baseline neutrophil:lymphocyte ratio may be predictive of immune-mediated response and warrants further investigation.
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    Diffusion weighted and dynamic contrast enhanced MRI as an imaging biomarker for stereotactic ablative body radiotherapy (SABR) of primary renal cell carcinoma
    Reynolds, HM ; Parameswaran, BK ; Finnegan, ME ; Roettger, D ; Lau, E ; Kron, T ; Shaw, M ; Chander, S ; Siva, S ; Dregely, I (PUBLIC LIBRARY SCIENCE, 2018-08-16)
    PURPOSE: To explore the utility of diffusion and perfusion changes in primary renal cell carcinoma (RCC) after stereotactic ablative body radiotherapy (SABR) as an early biomarker of treatment response, using diffusion weighted (DWI) and dynamic contrast enhanced (DCE) MRI. METHODS: Patients enrolled in a prospective pilot clinical trial received SABR for primary RCC, and had DWI and DCE MRI scheduled at baseline, 14 days and 70 days after SABR. Tumours <5cm diameter received a single fraction of 26 Gy and larger tumours received three fractions of 14 Gy. Apparent diffusion coefficient (ADC) maps were computed from DWI data and parametric and pharmacokinetic maps were fitted to the DCE data. Tumour volumes were contoured and statistics extracted. Spearman's rank correlation coefficients were computed between MRI parameter changes versus the percentage tumour volume change from CT at 6, 12 and 24 months and the last follow-up relative to baseline CT. RESULTS: Twelve patients were eligible for DWI analysis, and a subset of ten patients for DCE MRI analysis. DCE MRI from the second follow-up MRI scan showed correlations between the change in percentage voxels with washout contrast enhancement behaviour and the change in tumour volume (ρ = 0.84, p = 0.004 at 12 month CT, ρ = 0.81, p = 0.02 at 24 month CT, and ρ = 0.89, p = 0.001 at last follow-up CT). The change in mean initial rate of enhancement and mean Ktrans at the second follow-up MRI scan were positively correlated with percent tumour volume change at the 12 month CT onwards (ρ = 0.65, p = 0.05 and ρ = 0.66, p = 0.04 at 12 month CT respectively). Changes in ADC kurtosis from histogram analysis at the first follow-up MRI scan also showed positive correlations with the percentage tumour volume change (ρ = 0.66, p = 0.02 at 12 month CT, ρ = 0.69, p = 0.02 at last follow-up CT), but these results are possibly confounded by inflammation. CONCLUSION: DWI and DCE MRI parameters show potential as early response biomarkers after SABR for primary RCC. Further prospective validation using larger patient cohorts is warranted.
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    Acute toxicity in prostate cancer patients treated with and without image-guided radiotherapy
    Gill, S ; Thomas, J ; Fox, C ; Kron, T ; Rolfo, A ; Leahy, M ; Chander, S ; Williams, S ; Tai, KH ; Duchesne, GM ; Foroudi, F (BIOMED CENTRAL LTD, 2011-10-28)
    BACKGROUND: Image-guided radiotherapy (IGRT) increases the accuracy of treatment delivery through daily target localisation. We report on toxicity symptoms experienced during radiotherapy treatment, with and without IGRT in prostate cancer patients treated radically. METHODS: Between 2006 and 2009, acute toxicity data for ten symptoms were collected prospectively onto standardized assessment forms. Toxicity was scored during radiotherapy, according to the Common Terminology Criteria Adverse Events V3.0, for 275 prostate cancer patients before and after the implementation of a fiducial marker IGRT program and dose escalation from 74 Gy in 37 fractions, to 78 Gy in 39 fractions. Margins and planning constraints were maintained the same during the study period. The symptoms scored were urinary frequency, cystitis, bladder spasm, urinary incontinence, urinary retention, diarrhoea, haemorrhoids, proctitis, anal skin discomfort and fatigue. Analysis was conducted for the maximum grade of toxicity and the median number of days from the onset of that toxicity to the end of treatment. RESULTS: In the IGRT group, 14228 toxicity scores were analysed from 249 patients. In the non-IGRT group, 1893 toxicity scores were analysed from 26 patients. Urinary frequency ≥G3 affected 23% and 7% in the non-IGRT and IGRT group respectively (p = 0.0188). Diarrhoea ≥G2 affected 15% and 3% of patients in the non-IGRT and IGRT groups (p = 0.0174). Fatigue ≥G2 affected 23% and 8% of patients in the non-IGRT and IGRT groups (p = 0.0271). The median number of days with a toxicity was higher for ≥G2 (p = 0.0179) and ≥G3 frequency (p = 0.0027), ≥G2 diarrhoea (p = 0.0033) and ≥G2 fatigue (p = 0.0088) in the non-IGRT group compared to the IGRT group. Other toxicities were not of significant statistical difference. CONCLUSIONS: In this study, prostate cancer patients treated radically with IGRT had less severe urinary frequency, diarrhoea and fatigue during treatment compared to patients treated with non-IGRT. Onset of these symptoms was earlier in the non-IGRT group. IGRT results in less acute toxicity during radiotherapy in prostate cancer.
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    Seminal vesicle intrafraction motion analysed with cinematic magnetic resonance imaging
    Gill, S ; Dang, K ; Fox, C ; Bressel, M ; Kron, T ; Bergen, N ; Ferris, N ; Owen, R ; Chander, S ; Tai, KH ; Foroudi, F (BMC, 2014-08-08)
    PURPOSE: This study analyses seminal vesicle displacement relative to the prostate and in relation to treatment time. METHOD: A group of eleven patients undergoing prostate cancer radiotherapy were imaged with a continuous 3 T cine-MRI in the standard treatment setup position. Four images were recorded every 4 seconds for 15 minutes in the sagittal plane and every 6.5 seconds for 12 minutes in the coronal plane. The prostate gland and seminal vesicles were contoured on each MRI image. The coordinates of the centroid of the prostate and seminal vesicles on each image was analysed for displacement against time. Displacements between the 2.5 percentile and 97.5 percentile (i.e. the 2.5% trimmed range) for prostate and seminal vesicle centroid displacements were measured for 3, 5, 10 and 15 minutes time intervals in the anterior-posterior (AP), left-right (LR) and superior-inferior (SI) directions. Real time prostate and seminal vesicle displacement was compared for individual patients. RESULTS: The 2.5% trimmed range for 3, 5, 10 and 15 minutes for the seminal vesicle centroids in the SI direction measured 4.7 mm; 5.8 mm; 6.5 mm and 7.2 mm respectively. In the AP direction, it was 4.0 mm, 4.5 mm, 6.5 mm, and 7.0 mm. In the LR direction for 3, 5 and 10 minutes; for the left seminal vesicle, it was 2.7 mm, 2.8 mm, 3.4 mm and for the right seminal vesicle, it was 3.4 mm, 3.3 mm, and 3.4 mm. The correlation between the real-time prostate and seminal vesicle displacement varied substantially between patients indicating that the relationship between prostate displacement and seminal vesicles displacement is patient specific with the majority of the patients not having a strong relationship. CONCLUSION: Our study shows that seminal vesicle motion increases with treatment time, and that the prostate and seminal vesicle centroids do not move in unison in real time, and that an additional margin is required for independent seminal vesicle motion if treatment localisation is to the prostate.
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    Safety, Efficacy, and Patterns of Failure After Single-Fraction Stereotactic Body Radiation Therapy (SBRT) for Oligometastases
    Sogono, P ; Bressel, M ; David, S ; Shaw, M ; Chander, S ; Chu, J ; Plumridge, N ; Byrne, K ; Hardcastle, N ; Kron, T ; Wheeler, G ; Hanna, GG ; MacManus, M ; Ball, D ; Siva, S (ELSEVIER SCIENCE INC, 2021-03-01)
    PURPOSE: Fewer attendances for radiation therapy results in increased efficiency and less foot traffic within a radiation therapy department. We investigated outcomes after single-fraction (SF) stereotactic body radiation therapy (SBRT) in patients with oligometastatic disease. METHODS AND MATERIALS: Between February 2010 and June 2019, patients who received SF SBRT to 1 to 5 sites of oligometastatic disease were included in this retrospective study. The primary objective was to describe patterns of first failure after SBRT. Secondary objectives included overall survival (OS), progression-free survival (PFS), high-grade treatment-related toxicity (Common Terminology Criteria for Adverse Events grade ≥3), and freedom from systemic therapy (FFST). RESULTS: In total, 371 patients with 494 extracranial oligometastases received SF SBRT ranging from 16 Gy to 28 Gy. The most common primary malignancies were prostate (n = 107), lung (n = 63), kidney (n = 52), gastrointestinal (n = 51), and breast cancers (n = 42). The median follow-up was 3.1 years. The 1-, 3-, and 5-year OS was 93%, 69%, and 55%, respectively; PFS was 48%, 19%, and 14%, respectively; and FFST was 70%, 43%, and 35%, respectively. Twelve patients (3%) developed grade 3 to 4 treatment-related toxicity, with no grade 5 toxicity. As the first site of failure, the cumulative incidence of local failure (irrespective of other failures) at 1, 3 and 5 years was 4%, 8%, and 8%, respectively; locoregional relapse at the primary was 10%, 18%, and 18%, respectively; and distant failure was 45%, 66%, and 70%, respectively. CONCLUSIONS: SF SBRT is safe and effective, and a significant proportion of patients remain FFST for several years after therapy. This approach could be considered in resource-constrained or bundled-payment environments. Locoregional failure of the primary site is the second most common pattern of failure, suggesting a role for optimization of primary control during metastasis-directed therapy.
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    NaF PET/CT for response assessment of prostate cancer bone metastases treated with single fraction stereotactic ablative body radiotherapy
    Hardcastle, N ; Hofman, MS ; Lee, C-Y ; Callahan, J ; Selbie, L ; Foroudi, F ; Shaw, M ; Chander, S ; Lim, A ; Chesson, B ; Murphy, DG ; Kron, T ; Siva, S (BMC, 2019-09-05)
    INTRODUCTION: In prostate cancer patients, imaging of bone metastases is enhanced through the use of sodium fluoride positron emission tomography (18F-NaF PET/CT). This imaging technique shows areas of enhanced osteoblastic activity and blood flow. In this work, 18F-NaF PET/CT was investigated for response assessment to single fraction stereotactic ablative body radiotherapy (SABR) to bone metastases in prostate cancer patients. METHODS: Patients with bone metastases in a prospective trial treated with single fraction SABR received a 18F-NaF PET/CT scan prior to and 6 months post-SABR. The SUVmax in the tumour was determined and the difference between before and after SABR determined. The change in uptake in the non-tumour bone was also measured as a function of the received SABR dose. RESULTS: Reduction in SUVmax was observed in 29 of 33 lesions 6 months after SABR (mean absolute decrease in SUVmax 17.7, 95% CI 25.8 to - 9.4, p = 0.0001). Of the three lesions with increased SUVmax post-SABR, two were from the same patient and located in the vertebral column. Both were determined to be local progression in addition to one fracture. The third lesion (in a rib) was shown to be controlled locally but suffered from a fracture at 24 months. Progression adjacent to the treated volume was observed in two patients. The non-tumour bone irradiated showed increased loss in uptake with increasing dose, with a median loss in uptake of 23.3% for bone receiving 24 Gy. CONCLUSION: 18F-NaF PET/CT for response assessment of bone metastases to single fraction SABR indicates high rates of reduction of osteoblastic activity in the tumour and non-tumour bone receiving high doses. The occurrence of marginal recurrence indicates use of larger clinical target volumes may be warranted in treatment of bone metastases. TRIAL REGISTRATION: POPSTAR, 'Pilot Study of patients with Oligometastases from Prostate cancer treated with STereotactic Ablative Radiotherapy', Universal Trial Number U1111-1140-7563 , Registered 17th April 2013.