Sir Peter MacCallum Department of Oncology - Research Publications
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ItemImportance of quality in radiation oncology(WILEY, 2017-10)
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ItemStereotactic ablative body radiotherapy for inoperable primary kidney cancer: a prospective clinical trial(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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ItemA dosimetric comparison of 3D conformal vs intensity modulated vs volumetric arc radiation therapy for muscle invasive bladder cancer(BMC, 2012-07-23)BACKGROUND: To compare 3 Dimensional Conformal radiotherapy (3D-CRT) with Intensity Modulated Radiotherapy (IMRT) with Volumetric-Modulated Arc Therapy (VMAT) for bladder cancer. METHODS: Radiotherapy plans for 15 patients with T2-T4N0M0 bladder cancer were prospectively developed for 3-DCRT, IMRT and VMAT using Varian Eclipse planning system. The same radiation therapist carried out all planning and the same clinical dosimetric constraints were used. 10 of the patients with well localised tumours had a simultaneous infield boost (SIB) of the primary tumour planned for both IMRT and VMAT. Tumour control probabilities and normal tissue complication probabilities were calculated. RESULTS: Mean planning time for 3D-CRT, IMRT and VMAT was 30.0, 49.3, and 141.0 minutes respectively. The mean PTV conformity (CI) index for 3D-CRT was 1.32, for IMRT 1.05, and for VMAT 1.05. The PTV Homogeneity (HI) index was 0.080 for 3D-CRT, 0.073 for IMRT and 0.086 for VMAT. Tumour control and normal tissue complication probabilities were similar for 3D-CRT, IMRT and VMAT. The mean monitor units were 267 (range 250-293) for 3D-CRT; 824 (range 641-1083) for IMRT; and 403 (range 333-489) for VMAT (P < 0.05). Average treatment delivery time were 2:25min (range 2:01-3:09) for 3D-CRT; 4:39 (range 3:41-6:40) for IMRT; and 1:14 (range 1:13-1:14) for VMAT. In selected patients, the SIB did not result in a higher dose to small bowel or rectum. CONCLUSIONS: VMAT is associated with similar dosimetric advantages as IMRT over 3D-CRT for muscle invasive bladder cancer. VMAT is associated with faster delivery times and less number of mean monitor units than IMRT. SIB is feasible in selected patients with localized tumours.
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ItemSeminal vesicle interfraction displacement and margins in image guided radiotherapy for prostate cancer(BMC, 2012-08-13)BACKGROUND: To analyze interfraction motion of seminal vesicles (SV), and its motion relative to rectal and bladder filling. METHODS AND MATERIALS: SV and prostate were contoured on 771 daily computed tomography "on rails" scans from 24 prostate cancer patients undergoing radiotherapy. Random and systematic errors for SV centroid displacement were measured relative to the prostate centroid. Margins required for complete geometric coverage of SV were determined using isotropic expansion of reference contours. SV motion relative to rectum and bladder was determined. RESULTS: Systematic error for the SV was 1.9 mm left-right (LR), 2.9 mm anterior-posterior (AP) and 3.6 mm superior-inferior (SI). Random error was 1.4 mm (LR), 2.7 mm (AP) and 2.1 mm (SI). 10 mm margins covered the entire left SV and right SV on at least 90% of fractions in 50% and 33% of patients and 15 mm margins covered 88% and 79% respectively. SV AP movement correlated with movement of the most posterior point of the bladder (mean R2 = 0.46, SD = 0.24) and rectal area (mean R2 = 0.38, SD = 0.21). CONCLUSIONS: Considerable interfraction displacement of SV was observed in this cohort of patients. Bladder and rectal parameters correlated with SV movement.
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ItemAcute toxicity in prostate cancer patients treated with and without image-guided radiotherapy(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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ItemShort communication: timeline of radiation-induced kidney function loss after stereotactic ablative body radiotherapy of renal cell carcinoma as evaluated by serial 99mTc-DMSA SPECT/CT(BMC, 2014-11-26)BACKGROUND: Stereotactic ablative body radiotherapy (SABR) has been proposed as a definitive treatment for patients with inoperable primary renal cell carcinoma. However, there is little documentation detailing the radiobiological effects of hypofractionated radiation on healthy renal tissue. FINDINGS: In this study we describe a methodology for assessment of regional change in renal function in response to single fraction SABR of 26 Gy. In a patient with a solitary kidney, detailed follow-up of kidney function post-treatment was determined through 3-dimensional SPECT/CT imaging and (51)Cr-EDTA measurements. Based on measurements of glomerular filtration rate, renal function declined rapidly by 34% at 3 months, plateaued at 43% loss at 12 months, with minimal further decrease to 49% of baseline by 18 months. CONCLUSIONS: The pattern of renal functional change in (99m)Tc-DMSA uptake on SPECT/CT imaging correlates with dose delivered. This study demonstrates a dose effect relationship of SABR with loss of kidney function.
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ItemSeminal vesicle intrafraction motion analysed with cinematic magnetic resonance imaging(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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ItemAn analysis of respiratory induced kidney motion on four-dimensional computed tomography and its implications for stereotactic kidney radiotherapy(BIOMED CENTRAL LTD, 2013-10-26)BACKGROUND AND PURPOSE: Stereotactic ablative body radiotherapy (SABR) is an emerging treatment modality for primary renal cell carcinoma. To account for respiratory-induced target motion, an internal target volume (ITV) concept is often used in treatment planning of SABR. The purpose of this study is to assess patterns of kidney motion and investigate potential surrogates of kidney displacement with the view of ITV verification during treatment. MATERIAL AND METHODS: Datasets from 71 consecutive patients with free breathing four-dimensional computed tomography (4DCT) planning scans were included in this study. The displacement of the left and right hemi-diaphragm, liver dome and abdominal wall were measured and tested for correlation with the displacement of the both kidneys and patient breathing frequency. RESULTS: Nine patients were excluded due to severe banding artifact. Of 62 evaluable patients, the median age was 68 years, with 41 male patients and 21 female patients. The mean (range) of the maximum, minimum and average breathing frequency throughout the 4DCTs were 20.1 (11-38), 15.1 (9-24) and 17.3 (9-27.5) breaths per minute, respectively. The mean (interquartile range) displacement of the left and right kidneys was 0.74 cm (0.45-0.98 cm) and 0.75 cm (0.49-0.97) respectively. The amplitude of liver-dome motion was correlated with right kidney displacement (r=0.52, p<0.001), but not with left kidney displacement (p=0.796). There was a statistically significant correlation between the magnitude of right kidney displacement and that of abdominal displacement (r=0.36, p=0.004), but not the left kidney (r=0.24, p=0.056). Hemi-diaphragm displacements were correlated with kidney displacements respectively, with a weaker correlation for the left kidney/left diaphragm (r=0.45, [95% CI 0.22 to 0.63], p=<0.001) than for the right kidney/right diaphragm (r=0.57, [95% CI 0.37 to 0.72], p=<0.001). CONCLUSIONS: For the majority of patients, maximal left and right kidney displacement is subcentimeter in magnitude. The magnitude of kidney motion cannot be reliably estimated from the diaphragmatic, liver dome or abdominal wall surrogates. One explanation may be that the kidneys are not uniformly in contact with the surrogates investigated in this study. Further investigation is required before surrogates of kidney displacement are used for clinical SABR delivery.
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ItemGeographical miss of the prostate during image-guided radiotherapy with a 6-mm posterior expansion margin(WILEY, 2017-06)INTRODUCTION: Our department commonly uses a planning target volume (PTV) expansion of 6 mm posterior and 1 cm in all other directions when treating prostate cancer patients with image-guided radiotherapy (IGRT). This study aimed to test the adequacy of this PTV expansion by assessing geographical miss of the prostate on post-treatment cone-beam CT (CBCT) and identify those at risk of geographical miss. METHODS: Twenty-two prostate cancer patients receiving IGRT with implanted fiducial markers underwent daily pre-treatment orthogonal kV imaging followed by a post-treatment CBCT for a total of 432 fractions. The prostate was outlined on all CBCTs. For each imaging set, the volume of geographic miss was measured by subtracting the PTV from the planning CT and prostate volume on the post-treatment CBCT. RESULTS: The prostate volume moved outside the PTV by >0.01 cc in 9% of fractions (39/432). This occurred in 13 (59%) of 22 patients. Large prostates >40 cc and >50 cc had significantly more geographical miss events (both P < 0.001). Changes in rectal filling appear to be responsible for prostate motion/deformation in 82% (32/39) of fractions. CONCLUSIONS: Our analysis suggests that, despite IGRT, prostate PTV margins are not adequate in some patients, particularly those with large prostates. PTV margins may be reduced in some other patients. Prostate rotation and deformation play an important role in setting margins and may not always be represented accurately by fiducial marker displacements. Individualised and adaptive margins for prostate cancer patients should be a priority for future research.
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ItemNaF PET/CT for response assessment of prostate cancer bone metastases treated with single fraction stereotactic ablative body radiotherapy(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.