Evaluation of clinical and endoscopic toxicity after external beam radiotherapy and endorectal brachytherapy in elderly patients with rectal cancer treated in the HERBERT study.

INTRODUCTION: The HERBERT study evaluated a high-dose-rate endorectal brachytherapy boost (HDREBT) after EBRT in medically inoperable/elderly patients with rectal cancer. The response-rates are promising but not without risk of toxicity. The current analysis provides a comprehensive overview of patient reported, physician reported and endoscopically observed toxicity. MATERIAL AND METHODS: A brachytherapy dose finding study was performed in 38 inoperable/elderly patients with T2-T4N0-1 rectal cancer. Patients received EBRT (13 × 3 Gy) followed by three weekly HDREBT applications (5-8 Gy). Toxicity was assessed via three methods: patient and physician (CTCAEv3) reported rectal symptoms and endoscopically. Wilcoxon's signed rank test, paired t-test and Spearman's correlation were used. RESULTS: Patient reported bowel symptoms showed a marked increase at the end of EBRT and two weeks after HDREBT. Acute grade 2 and 3 proctitis occurred in 68.4% and 13.2% respectively while late grade 2 and ≥3 proctitis occurred in 48% and 40%. Endoscopic evaluation mainly showed erythema and telangiectasia. In three patients frank haemorrhage or ulceration occurred. Most severe toxicity was observed 12-18 months after treatment. CONCLUSION: For elderly patients with rectal cancer, definitive radiotherapy can provide good tumour response but has a substantial risk of toxicity. The potential benefit and risks of a HDREBT boost above EBRT alone must be further evaluated.

Treatment plan adaptation for MRI-guided radiotherapy using solely MRI data: a CT-based simulation study.

An integrated MRI-accelerator system provides MRI images before and during irradiation. Our purpose is to investigate the feasibility of treatment plan adaptation using solely MRI data, which lack density information. In this study we used CT data to quantify the tissue density effect. Treatment planning was performed for five prostate cancer patients. We simulated correction of a 3, 5, 7 and 10 mm prostate shift relative to the body contour in the anterior, posterior, superior and inferior directions. We applied the original treatment plan to each corrected prostate shift and recalculated the dose distribution using the same monitor units (MU). We calculated the dose differences with and without density information. The latter mimics geometrically correct MRI data. Physical path lengths, available in MRI data, are used to perform MU rescaling per beam and are shown to be of more importance than tissue densities for treatment plan adaptation in prostate cancer. As the change in the physical path length of the central beam axis is representative of the entire beam, MU rescaling based on central beam axis information works fine. In conclusion, MRI data could be used for treatment plan adaptation in prostate cancer provided that the images are geometrically correct.

Contour propagation in MRI-guided radiotherapy treatment of cervical cancer: the accuracy of rigid, non-rigid and semi-automatic registrations.

External beam radiation treatment for patients with cervical cancer is hindered by the relatively large motion of the target volume. A hybrid MRI-accelerator system makes it possible to acquire online MR images during treatment in order to correct for motion and deformation. To fully benefit from such a system, online delineation of the target volumes is necessary. The aim of this study is to investigate the accuracy of rigid, non-rigid and semi-automatic registrations of MR images for interfractional contour propagation in patients with cervical cancer. Registration using mutual information was performed on both bony anatomy and soft tissue. A B-spline transform was used for the non-rigid method. Semi-automatic registration was implemented with a point set registration algorithm on a small set of manual landmarks. Online registration was simulated by application of each method to four weekly MRI scans for each of 33 cervical cancer patients. Evaluation was performed by distance analysis with respect to manual delineations. The results show that soft-tissue registration significantly (P < 0.001) improves the accuracy of contour propagation compared to registration based on bony anatomy. A combination of user-assisted and non-rigid registration provides the best results with a median error of 3.2 mm (1.4-9.9 mm) compared to 5.9 mm (1.7-19.7 mm) with bone registration (P < 0.001) and 3.4 mm (1.3-19.1 mm) with non-rigid registration (P = 0.01). In a clinical setting, the benefit may be further increased when outliers can be removed by visual inspection of the online images. We conclude that for external beam radiation treatment of cervical cancer, online MRI imaging will allow target localization based on soft tissue visualization, which provides a significantly higher accuracy than localization based on bony anatomy. The use of limited user input to guide the registration increases overall accuracy. Additional non-rigid registration further reduces the propagation error and negates errors caused by small observer variations.

Integrating a 1.5 T MRI scanner with a 6 MV accelerator: proof of concept.

At the UMC Utrecht, The Netherlands, we have constructed a prototype MRI accelerator. The prototype is a modified 6 MV Elekta (Crawley, UK) accelerator next to a modified 1.5 T Philips Achieva (Best, The Netherlands) MRI system. From the initial design onwards, modifications to both systems were aimed to yield simultaneous and unhampered operation of the MRI and the accelerator. Indeed, the simultaneous operation is shown by performing diagnostic quality 1.5 T MRI with the radiation beam on. No degradation of the performance of either system was found. The integrated 1.5 T MRI system and radiotherapy accelerator allow simultaneous irradiation and MR imaging. The full diagnostic imaging capacities of the MRI can be used; dedicated sequences for MRI-guided radiotherapy treatments will be developed. This proof of concept opens the door towards a clinical prototype to start testing MRI-guided radiation therapy (MRIgRT) in the clinic.

Variation in target and rectum dose due to prostate deformation: an assessment by repeated MR imaging and treatment planning.

In daily clinical practice, implanted fiducial markers are used to correct for prostate motion, but not for prostate deformation. The aim of this study is to investigate the variation in target and rectum dose due to the deformation of the prostate gland (without seminal vesicles). Therefore, we performed five to six MRI scans of eight healthy volunteers that exhibited large variation in rectal volume and thus prostate deformation. Prostate motion was corrected by a mask-based rigid registration which uses the delineation as well as the internal structures of the prostate gland. Per MRI scan, one IMRT plan with a PTV margin of 4 mm was created, resulting in 41 IMRT plans. The dose distribution of the IMRT plan based on the MRI scan with the minimum rectal volume was applied to the other rigidly registered MRI scans to evaluate the impact of prostate deformation. In conclusion, pre-treatment planning on the minimum rectal volume can cause a fraction dose increase (up to 15%) to the rectum due to prostate deformation. The impact on the total dose increase to the rectum depends on the intrapatient rectum variation during treatment, but is negligible with the currently used PTV margins in a fractionated treatment.

A novel method for comparing 3D target volume delineations in radiotherapy.

When comparing delineations it is often useful to obtain a local measure of distance between the volume surfaces. Commonly used methods for analysing local distance exhibit fundamental drawbacks which may cause overestimation of the distance or lead to asymmetry in the measure. This paper describes a new method that aims to solve these problems. The new method finds corresponding points between two delineations by traversing a vector field based on the combined gradient of the distance transforms. The proposed method provides a fundamentally more reliable, symmetric measure of distance. This is supported by an illustrative example of observer variation in prostate delineation. An implementation of the method is available on request to the author.