Dose-escalated radiotherapy to 82 Gy for prostate cancer following insertion of a peri-rectal hydrogel spacer: 3-year outcomes from a phase II trial.

BACKGROUND: Dose-escalation to above 80 Gy during external beam radiotherapy for localised prostate cancer leads to improved oncological outcomes but also substantially increased rectal toxicity. The aim of this study was to demonstrate the safety and efficacy of escalating the dose to 82 Gy following insertion of a peri-rectal hydrogel spacer (HS) prior to radiotherapy. METHODS: This was a single arm, open-label, prospective study of men with localised prostate cancer who were prescribed a course of intensity modulated radiotherapy escalated to 82 Gy in 2 Gy fractions following insertion of the SpaceOAR™ HS (Boston Scientific, Marlborough, MA). Patients were prescribed a standard course of 78 Gy in 2 Gy fractions where rectal dose constraints could not be met for the 82 Gy plan. The co-primary endpoints were the rate of grade 3 gastrointestinal (GI) and genitourinary (GU) adverse events (CTCAE, v4), and patient-reported quality of life (QoL) (EORTC QLQ-C30 and PR25 modules), up to 37.5 months post-treatment. RESULTS: Seventy patients received treatment on the study, with 64 (91.4%) receiving an 82 Gy treatment course. The median follow-up time post-treatment was 37.4 months. The rate of radiotherapy-related grade 3 GI and GU adverse events was 0% and 2.9%, respectively. There were 2 (2.9%) grade 3 adverse events related to insertion of the HS. Only small and transient declines in QoL were observed; there was no clinically or statistically significant decline in QoL beyond 13.5 months and up to 37.5 months post-treatment, compared to baseline. No late RTOG-defined grade ≥ 2 GI toxicity was observed, with no GI toxicity observed in any patient at 37.5 months post-treatment. Nine (12.9%) patients met criteria for biochemical failure within the follow-up period. CONCLUSIONS: Dose-escalation to 82 Gy, facilitated by use of a hydrogel spacer, is safe and feasible, with minimal toxicity up to 37.5 months post-treatment when compared to rates of rectal toxicity in previous dose-escalation trials up to 80 Gy. Trials with longer follow-up of oncological and functional outcomes are required to robustly demonstrate a sustained widening of the therapeutic window. Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12621000056897 , 22/01/2021. Retrospectively registered.

The cardiac dose-sparing benefits of deep inspiration breath-hold in left breast irradiation: a systematic review.

INTRODUCTION: Despite technical advancements in breast radiation therapy, cardiac structures are still subject to significant levels of irradiation. As the use of adjuvant radiation therapy after breast-conserving surgery continues to improve survival for early breast cancer patients, the associated radiation-induced cardiac toxicities become increasingly relevant. Our primary aim was to evaluate the cardiac-sparing benefits of the deep inspiration breath-hold (DIBH) technique. METHODS: An electronic literature search of the PubMed database from 1966 to July 2014 was used to identify articles published in English relating to the dosimetric benefits of DIBH. Studies comparing the mean heart dose of DIBH and free breathing treatment plans for left breast cancer patients were eligible to be included in the review. Studies evaluating the reproducibility and stability of the DIBH technique were also reviewed. RESULTS: Ten studies provided data on the benefits of DIBH during left breast irradiation. From these studies, DIBH reduced the mean heart dose by up to 3.4 Gy when compared to a free breathing approach. Four studies reported that the DIBH technique was stable and reproducible on a daily basis. According to current estimates of the excess cardiac toxicity associated with radiation therapy, a 3.4 Gy reduction in mean heart dose is equivalent to a 13.6% reduction in the projected increase in risk of heart disease. CONCLUSION: DIBH is a reproducible and stable technique for left breast irradiation showing significant promise in reducing the late cardiac toxicities associated with radiation therapy.

Results of patient specific quality assurance for patients undergoing stereotactic ablative radiotherapy for lung lesions.

Hypofractionated image guided radiotherapy of extracranial targets has become increasingly popular as a treatment modality for inoperable patients with one or more small lesions, often referred to as stereotactic ablative body radiotherapy (SABR). This report details the results of the physical quality assurance (QA) program used for the first 33 lung cancer SABR radiotherapy 3D conformal treatment plans in our centre. SABR involves one or few fractions of high radiation dose delivered in many small fields or arcs with tight margins to mobile targets often delivered through heterogeneous media with non-coplanar beams. We have conducted patient-specific QA similar to the more common intensity modulated radiotherapy QA with particular reference to motion management. Individual patient QA was performed in a Perspex phantom using point dose verification with an ionisation chamber and radiochromic film for verification of the dose distribution both with static and moving detectors to verify motion management strategies. While individual beams could vary by up to 7%, the total dose in the target was found to be within ±2% of the prescribed dose for all 33 plans. Film measurements showed qualitative and quantitative agreement between planned and measured isodose line shapes and dimensions. The QA process highlighted the need to account for couch transmission and demonstrated that the ITV construction was appropriate for the treatment technique used. QA is essential for complex radiotherapy deliveries such as SABR. We found individual patient QA helpful in setting up the technique and understanding potential weaknesses in SABR workflow, thus providing confidence in SABR delivery.

Validation of a 4D-PET maximum intensity projection for delineation of an internal target volume.

PURPOSE: The delineation of internal target volumes (ITVs) in radiation therapy of lung tumors is currently performed by use of either free-breathing (FB) (18)F-fluorodeoxyglucose-positron emission tomography-computed tomography (FDG-PET/CT) or 4-dimensional (4D)-CT maximum intensity projection (MIP). In this report we validate the use of 4D-PET-MIP for the delineation of target volumes in both a phantom and in patients. METHODS AND MATERIALS: A phantom with 3 hollow spheres was prepared surrounded by air then water. The spheres and water background were filled with a mixture of (18)F and radiographic contrast medium. A 4D-PET/CT scan was performed of the phantom while moving in 4 different breathing patterns using a programmable motion device. Nine patients with an FDG-avid lung tumor who underwent FB and 4D-PET/CT and >5 mm of tumor motion were included for analysis. The 3 spheres and patient lesions were contoured by 2 contouring methods (40% of maximum and PET edge) on the FB-PET, FB-CT, 4D-PET, 4D-PET-MIP, and 4D-CT-MIP. The concordance between the different contoured volumes was calculated using a Dice coefficient (DC). The difference in lung tumor volumes between FB-PET and 4D-PET volumes was also measured. RESULTS: The average DC in the phantom using 40% and PET edge, respectively, was lowest for FB-PET/CT (DCAir = 0.72/0.67, DCBackground 0.63/0.62) and highest for 4D-PET/CT-MIP (DCAir = 0.84/0.83, DCBackground = 0.78/0.73). The average DC in the 9 patients using 40% and PET edge, respectively, was also lowest for FB-PET/CT (DC = 0.45/0.44) and highest for 4D-PET/CT-MIP (DC = 0.72/0.73). In the 9 lesions, the target volumes of the FB-PET using 40% and PET edge, respectively, were on average 40% and 45% smaller than the 4D-PET-MIP. CONCLUSION: A 4D-PET-MIP produces volumes with the highest concordance with 4D-CT-MIP across multiple breathing patterns and lesion sizes in both a phantom and among patients. Freebreathing PET/CT consistently underestimates ITV when compared with 4D PET/CT for a lesion affected by respiration.

Implementation of a lung radiosurgery program: technical considerations and quality assurance in an Australian institution.

INTRODUCTION: The Peter MacCallum Cancer Centre has established a stereotactic lung radiosurgery program for the treatment of isolated lung metastases. The aim of this study was to critically assess the technical feasibility of performing stereotactic lung radiosurgery in an Australian institution. METHODS: A single 26-Gy fraction of radiotherapy was delivered to patients with positron emission tomography (PET) staged solitary lung metastases. Motion management was addressed using four-dimensional computed tomographic simulation, and cone beam CT (CBCT) online soft-tissue matching. Treatments were with multiple coplanar and non-coplanar asymmetric beams. Patients were immobilised in a dedicated stereotactic body cradle. Quality assurance (QA) of treatment plans with both ion chamber and film measurements was performed accounting for patient-specific respiratory motion. RESULTS: Between February 2010 and February 2011, nine patients received stereotactic lung radiosurgery. One grade 1 toxicity and one grade 2 toxicity were recorded after treatment. The mean planning target volume was 22.6 cc. A median of eight beams were delivered per treatment plan (range 7-10) with a median of two non-coplanar beams (range 0-6). At treatment plan QA, the difference between planned and delivered dose was ≤1.76% in all static and dynamic ion chamber recordings. A mid-treatment CBCT was performed at a median time of 21 min, with the mean displacement discrepancy from initial set-up being 0.4 mm (range 0-2 mm). CONCLUSIONS: Stereotactic radiosurgery to the lung was both feasible and tolerable at our institution. Intrafractional immobilisation within 2 mm was reproducible. Excellent concordance between planned and delivered treatments was achieved in the phantom QA.