Image guided radiotherapy in curative treatment for prostate cancer. 5-year results from a randomized controlled trial (RIC-trial).

BACKGROUND: Between 2012 and 2015 we conducted a randomized controlled trial in prostate cancer patients comparing weekly 2-D portal imaging versus daily 3-D verification. AIM: To evaluate the clinical outcomes of image guided radiotherapy by presenting rectal and urinary side effects, health related quality of life and progression free survival after 5-years follow up of a randomized controlled trial. METHODS: We randomized 260 men with intermediate or high-risk prostate cancer to weekly 2-D portal imaging with 15 mm margin from CTV to PTV (Arm A) or daily 3-D cone-beam computer tomography with 7 mm margins (Arm B). Prescribed doses were 78 Gy/39 fractions. All patients received hormonal therapy. Primary end point was patient reported bowel symptoms and secondary outcomes were patient reported urinary symptoms, health- related quality of life and progression free survival. RESULTS: Of the 216 patients available for analyses at 5 years more than 90 % completed patient reported outcome measures. There were no significant differences between study arms for any single items nor scales evaluating bowel symptoms. There were also no differences in self-reported urinary symptoms nor in health-related quality of life. Symptom scores were low in both study arms. Progression free survival was similar in Arm B as compared to arm A (Hazard ratio 1.01; 95 % CI 0.57 to 1.97). CONCLUSIONS: Our results support that both 2-D weekly and 3-D daily image guided radiotherapy are safe and efficient treatments for PC and emphasize the need to evaluate technological progress in clinical trials with long follow-up.

Clinical experience of volumetric-modulated flattening filter free stereotactic body radiation therapy of lesions in the lung with deep inspiration breath-hold.

This clinical study aimed to evaluate lung cancer patients' ability to perform deep inspiration breath-hold (DIBH) during CT simulation and throughout the treatment course of stereotactic body radiation therapy (SBRT). In addition, target sizes, organ at risk (OAR) sizes, and doses to the respective volumes in filter-free volumetric-modulated arc therapy plans performed under free-breathing (FB) and DIBH conditions were evaluated. Twenty-one patients with peripheral lesions were included, of which 13 were eligible for SBRT. All patients underwent training for breath-hold during CT, and if they complied with the requirements, two CT scans were obtained: CT scan in DIBH and a four-dimensional CT scan in FB. The treatment plans in FB and DIBH were generated, and the dose parameters and volume sizes were compared. The endpoints for evaluation were patient compliance, target dose coverage, and doses to the OARs. This clinical study showed high patient DIBH compliance during both CT simulation and treatment for patients with lung cancer. A significant reduction in target volumes was achieved with SBRT in DIBH, in addition to significantly decreased doses to the heart, chest wall, and lungs. DIBH in SBRT of lung lesions is feasible, and a routine to manage intra-fractional deviation should be established upon implementation.

Training, validation, and clinical implementation of a deep-learning segmentation model for radiotherapy of loco-regional breast cancer.

AIM: To train and validate a comprehensive deep-learning (DL) segmentation model for loco-regional breast cancer with the aim of clinical implementation. METHODS: DL segmentation models for 7 clinical target volumes (CTVs) and 11 organs at risk (OARs) were trained on 170 left-sided breast cancer cases from two radiotherapy centres in Norway. Another 30 patient cases were used for validation, which included the evaluation of Dice similarity coefficient and Hausdorff distance, qualitative scoring according to clinical usability, and relevant dosimetric parameters. The manual inter-observer variation (IOV) was also evaluated and served as a benchmark. Delineation of the target volumes followed the ESTRO guidelines. RESULTS: Based on the geometric similarity metrics, the model performed significantly better than IOV for most structures. Qualitatively, no or only minor corrections were required for 14% and 71% of the CTVs and 72% and 26% of the OARs, respectively. Major corrections were required for 15% of the CTVs and 2% of the OARs. The most frequent corrections occurred in the cranial and caudal parts of the structures. The dose coverage, based on D98 > 95%, was fulfilled for 100% and 89% of the breast and lymph node CTVs, respectively. No differences in OAR dose parameters were considered clinically relevant. The model was implemented in a commercial treatment planning system, which generates the structures in 1.5 min. CONCLUSION: Convincing results from the validation led to the decision of clinical implementation. The clinical use will be monitored regarding applicability, standardization and efficiency.

Free breathing VMAT versus deep inspiration breath-hold 3D conformal radiation therapy for early stage left-sided breast cancer.

The purpose of the in silico study was to compare free breathing volumetric modulated arc therapy (VMAT) to standard deep inspiration breath-hold (DIBH) three-dimensional conformal radiotherapy (3DCRT) and determine whether the former is a viable option for elderly patients with left-sided early stage breast cancer. Data from 22 patients with early-stage left breast carcinoma requiring breast-only radiation therapy were used for this planning study. The robustness of VMAT plans when using the free breathing method was compared to that of standard 3DCRT plans using the DIBH method. The endpoints for evaluation were the target dose coverage as well as doses to the organs-at-risk. The free breathing VMAT plans produced a significantly higher mean dose to the heart and right breast than the DIBH-3DCRT plans. Free breathing VMAT plans resulted in significantly better target coverage than did 3DCRT using DIBH. The external volume that received more than 40 Gy was significantly smaller in the VMAT plans. Free breathing VMAT is a viable alternative to DIBH 3DCRT in elderly patients with a limited life expectancy and in subjects who are unable to perform DIBH. The choice of treatment should be individualized, and all relevant risks ought to be considered.

Dosimetric impact of interobserver variability in MRI-based delineation for cervical cancer brachytherapy.

PURPOSE AND BACKGROUND: To study the dosimetric impact of interobserver delineation variability (IODV) in MRI-based cervical cancer brachytherapy. MATERIALS AND METHODS: MR images of six patients were distributed to 10 experienced observers worldwide. They were asked to delineate the target volumes and the organs at risk (OARs) for each patient. Two types of reference contours were created (Expert Consensus - EC and Simultaneous Truth and Performance Level Estimation - STAPLE). Optimised plans based on both EC- and STAPLE-contours were prepared. These plans were transferred to each of the observer contour sets and the resulting DVH parameters (D(90) and D(2cc)) were calculated. For each patient the standard deviation (SD) for the 10 observers was calculated. RESULTS: A mean relative SD of 8-10% was found for GTV and High Risk CTV (HR-CTV) D(90) analysing one single fraction. For rectum and bladder the mean relative SD for D(2cc) was 5-8% while sigmoid was at 11%. For the whole treatment the IODV in HR-CTV caused an uncertainty of ±5 Gy(α/ß=10) (1SD). The corresponding figure for OARs was ±2-3 Gy(α/ß=3). The results were not sensitive as to which structure set was used for the optimisation. CONCLUSIONS: For the target volumes the dosimetric impact of IODV was smallest for the GTV and HR-CTV, while IODV had an even smaller impact on the bladder and rectum.

Radiation doses to Norwegian heart-transplanted patients undergoing annual coronary angiography.

Heart-transplanted patients in Norway undergo annual coronary angiography (CA). The aims of this study were to establish a conversion factor between dose-area product and effective dose for these examinations and to use this to evaluate the accumulated radiation dose and risks associated with annual CA. An experienced cardiac interventionist performed a simulated examination on an Alderson phantom loaded with thermoluminescence dosemeters. The simulated CA examination yielded a dose-area product of 17 Gy cm(2) and an effective dose of 3.4 mSv: the conversion factor between dose-area product and effective dose was 0.20 mSv Gy cm(-2). Dose-area product values from 200 heart-transplanted patients that had undergone 906 CA examinations between 2001 and 2008 were retrieved from the institutional database. Mean dose-area product from annual CA was 25 Gy cm(2), ranging from 2 to 140 Gy cm(2). Mean number of CA procedure was 8 (range, 1-23). Mean accumulated effective dose for Norwegian heart-transplanted patients between 2001 and 2008 was 34 mSv (range, 5-113 mSv). Doses and radiation risks for heart-transplanted patients are generally low, because most heart transplantations are performed on middle-aged patients with limited life expectancy. Special concern should however be taken to reduce doses for young heart-transplanted patients who are committed to lifelong follow-up of their transplanted heart.

Adaptive radiotherapy based on contrast enhanced cone beam CT imaging.

Cone beam CT (CBCT) imaging has become an integral part of radiation therapy, with images typically used for offline or online patient setup corrections based on bony anatomy co-registration. Ideally, the co-registration should be based on tumor localization. However, soft tissue contrast in CBCT images may be limited. In the present work, contrast enhanced CBCT (CECBCT) images were used for tumor visualization and treatment adaptation. Material and methods. A spontaneous canine maxillary tumor was subjected to repeated cone beam CT imaging during fractionated radiotherapy (10 fractions in total). At five of the treatment fractions, CECBCT images, employing an iodinated contrast agent, were acquired, as well as pre-contrast CBCT images. The tumor was clearly visible in post-contrast minus pre-contrast subtraction images, and these contrast images were used to delineate gross tumor volumes. IMRT dose plans were subsequently generated. Four different strategies were explored: 1) fully adapted planning based on each CECBCT image series, 2) planning based on images acquired at the first treatment fraction and patient repositioning following bony anatomy co-registration, 3) as for 2), but with patient repositioning based on co-registering contrast images, and 4) a strategy with no patient repositioning or treatment adaptation. The equivalent uniform dose (EUD) and tumor control probability (TCP) calculations to estimate treatment outcome for each strategy. Results. Similar translation vectors were found when bony anatomy and contrast enhancement co-registration were compared. Strategy 1 gave EUDs closest to the prescription dose and the highest TCP. Strategies 2 and 3 gave EUDs and TCPs close to that of strategy 1, with strategy 3 being slightly better than strategy 2. Even greater benefits from strategies 1 and 3 are expected with increasing tumor movement or deformation during treatment. The non-adaptive strategy 4 was clearly inferior to all three adaptive strategies. Conclusion. CECBCT may prove useful for adaptive radiotherapy.

The performance of multileaf collimators evaluated by the stripe test.

The performance of 3 multileaf collimator (MLC) systems (Varian Medical Systems, Elekta, and Siemens Medical Solutions) mounted on 7 different radiotherapy linear accelerators was investigated by a stripe test. The stripe test consisted of 8 adjacent multileaf segments of 2.5 x 40 cm(2), enclosed by all leaf pairs. With 6-MV photons, the segments were used to irradiate Agfa CR films. The optical density profile of the irradiated film in the travel direction of the MLC was used to estimate the short- and long-term leaf positioning reproducibility. The short-term reproducibility was found by analyzing 6 consecutive stripe tests. The long-term reproducibility was obtained by performing 3 to 5 stripe tests over 2 months. The short-term reproducibility was mainly within 0.3 mm for all systems. For the long-term reproducibility, the Varian and Elekta MLCs were within 0.4 to 0.5 mm, while the Siemens MLC showed a wider distribution, with values up to 1 mm for some leaf pairs. The inferior long-term reproducibility of the Siemens MLCs was mainly due to a decrease of the segment size with time. In conclusion, the stripe test is a useful method for evaluating MLC performance. Furthermore, the long-term reproducibility varied among the MLC systems investigated.