Marius Røthe Arnesen

Optimal treatment margins for radiotherapy of prostate cancer based on interfraction imaging

Purpose. To present a methodology to estimate optimal treatment margins for radiotherapy of prostate cancer based on interfraction imaging. Materials and methods. Cone beam CT images of a prostate cancer patient undergoing fractionated radiotherapy were acquired at all treatment sessions. The clinical target volume (CTV) and organs at risk (OARs; bladder and rectum) were delineated in the images. Random sampling from the CTV-OAR library was performed in order to simulate fractionated radiotherapy including intra- and interpatient variability in setup and organ motion/deformation. For each simulated patient, four treatment fields defined by multileaf collimators were automatically generated around the planning CTV. The treatment margin (the distance from the CTV to the field border) was varied between 2.5 and 20mm. Resulting dose distributions were calculated by a convolution method. Doses to OARs were reconstructed by polynomial warping, while the CTV was assumed to be a rigid body. The equivalent uniform dose (EUD), the tumor control probability (TCP) and the normal tissue complication probability (NTCP) were used to estimate the clinical effect. Patient repositioning strategies at treatment were compared. Results. The simulations produced population based EUD histograms for the CTV and the OARs. The number of patients receiving an optimal target EUD increased with increasing margins, but at the cost of an increasing number receiving a high EUD to the OARs. Calculations of the probability of complication-free tumor control and subsequent analysis gave an optimal treatment margin of about 10mm for the simulated population, if no correction strategy was undertaken. Conclusions. The current work illustrates the principle of optimal treatment margins based on interfraction imaging. Clinically applicable margins may be obtained if a large patient image database is available.

Serial diffusion tensor imaging for early detection of radiation‐induced injuries to normal‐appearing white matter in high‐grade glioma patients

To study the potential of diffusion tensor imaging (DTI) to serve as a biomarker for radiation‐induced brain injury during chemo‐radiotherapy (RT) treatment.

Dosimetric impact of a frame-based strategy in stereotactic radiotherapy of lung tumors

Abstract Introduction. Technological innovations have taken stereotactic body radiotherapy (SBRT) from frame-based strategies to image-guided strategies. In this study, cone beam computed tomography (CBCT) images acquired prior to SBRT of patients with lung tumors was used to study the dosimetric impact of a pure frame-based strategy. Material and methods. Thirty patients with inoperable lung tumors were retrospectively analyzed. All patients had received CBCT-guided SBRT with 3 fractions of 15 Gy to the planning target volume (PTV) margin including immobilization in a stereotactic body frame (SBF). Using the set-up corrections from the co-registration of the CBCT with the planning CT, all individual dose plans were recalculated with an isocenter position equal to the initial set-up position. Dose Volume Histogram (DVH) parameters of the recalculated dose plans were then analyzed. Results. The simulated plans showed that 88% of all fractions resulted in minimum 14.5 Gy to the internal target volume (ITV). For the simulated summed treatment (3 fractions per patient), 83% of the patients would minimum receive the prescription dose (45 Gy) to 100% of the ITV and all except one would receive the prescription dose to more than 90% of the ITV. Conclusions. SBRT including SBF, but without image guidance, results in appropriate dose coverage in most cases, using the current margins. With image guidance, margins for SBRT of lung tumors could possibly be reduced.

Dose painting by numbers in a standard treatment planning system using inverted dose prescription maps

ABSTRACT Background. Dose painting by numbers (DPBN) is a method to deliver an inhomogeneous tumor dose voxel-by-voxel with a prescription based on biological medical images. However, planning of DPBN is not supported by commercial treatment planning systems (TPS) today. Here, a straightforward method for DPBN with a standard TPS is presented. Material and methods. DPBN tumor dose prescription maps were generated from 18F-FDG-PET images applying a linear relationship between image voxel value and dose. An inverted DPBN prescription map was created and imported into a standard TPS where it was defined as a mock pre-treated dose. Using inverse optimization for the summed dose, a planned DPBN dose distribution was created. The procedure was tested in standard TPS for three different tumor cases; cervix, lung and head and neck. The treatment plans were compared to the prescribed DPBN dose distribution by three-dimensional (3D) gamma analysis and quality factors (QFs). Delivery of the DPBN plans was assessed with portal dosimetry (PD). Results. Maximum tumor doses of 149%, 140% and 151% relative to the minimum tumor dose were prescribed for the cervix, lung and head and neck case, respectively. DPBN distributions were well achieved within the tumor whilst normal tissue doses were within constraints. Generally, high gamma pass rates (> 89% at 2%/2 mm) and low QFs (< 2.6%) were found. PD showed that all DPBN plans could be successfully delivered. Conclusions. The presented methodology enables the use of currently available TPSs for DPBN planning and delivery and may therefore pave the way for clinical implementation.

Spatial dosimetric sensitivity of contouring uncertainties in gynecological 3D-based brachytherapy

BACKGROUND AND PURPOSE This study aims to analyze subsections of the target volume that are sensitive to delineation uncertainties with respect to underdosage (spatial dosimetric uncertainty) in MRI-based brachytherapy of cervical cancer. MATERIAL AND METHODS A methodology was developed to simulate delineation uncertainties by shifting an angular segment of the contour perpendicular to the original HR-CTV. For shifts of 3, 6 and 9mm resulting D90 and D98 were calculated for the modified contour. The sensitivity of the dose plan to the locally introduced error was estimated by linear regression of D90 or D98 against the magnitude of the shift. The methodology was employed on 20 patients treated with tandem ring brachytherapy. RESULTS Topographic maps resulting from the dosimetric sensitivity analysis showed both large spatial variations and substantial inter-patient variations. For all plans included the spatial sensitivity in D90 ranged from 0.0 to -1.6%/mm, correspondingly sensitivity in D98 ranged from 0 to -4.6%/mm. A significantly increased dosimetric sensitivity was found in anterior direction and the cranial part of the tumor (p<0.05). CONCLUSIONS The developed methodology identifies specific tumor regions and patients with increased risk of underdosage from delineation uncertainties in brachytherapy of cervical cancer.

Impact of dose escalation and adaptive radiotherapy for cervical cancers on tumour shrinkage - A modelling study

Tumour shrinkage occurs during fractionated radiotherapy and is regulated by radiation induced cellular damage, repopulation of viable cells and clearance of dead cells. In some cases additional tumour shrinkage during external beam therapy may be beneficial, particularly for locally advanced cervical cancer where a small tumour volume may simplify and improve brachytherapy. In the current work, a mathematical tumour model is utilized to investigate how local dose escalation affects tumour shrinkage, focusing on implications for brachytherapy. The iterative two-compartment model is based upon linear-quadratic radiation response, a doubling time for viable cells and a half-time for clearance of dead cells. The model was individually fitted to clinical tumour volume data from fractionated radiotherapy of 25 cervical cancer patients. Three different fractionation patterns for dose escalation, all with an additional dose of 12.2 Gy, were simulated and compared to standard fractionation in terms of tumour shrinkage. An adaptive strategy where dose escalation was initiated after one week of treatment was also considered. For 22 out of 25 patients, a good model fit was achieved to the observed tumour shrinkage. A large degree of inter-patient variation was seen in predicted volume reduction following dose escalation. For the 10 best responding patients, a mean tumour volume reduction of 34  ±  3% (relative to standard treatment) was estimated at the time of brachytherapy. Timing of initiating dose escalation had a larger impact than the number of fractions applied. In conclusion, the model was found useful in evaluating the impact from dose escalation on tumour shrinkage. The results indicate that dose escalation could be conducted from the start of external beam radiotherapy in order to obtain additional tumour shrinkage before brachytherapy.

Combining radioiodine and external beam radiation therapy: the potential of integrated treatment planning for differentiated thyroid cancer

Lars Tore Gyland Mikalsen , Marius Røthe Arnesen , Trond Velde Bogsrud, Einar Dale and Caroline Stokke Department of Diagnostic Physics, Oslo University Hospital, Oslo, Norway; Department of Medical Physics, Oslo University Hospital, Oslo, Norway; Department of Nuclear Medicine, Oslo University Hospital, Oslo, Norway; Department of Oncology, Oslo University Hospital, Oslo, Norway; Department of Life Sciences and Health, Oslo and Akershus University College of Applied Science, Oslo, Norway

EP-1439: IMRT and IMPT of cervical cancer and effect of reduced margins

Purpose/Objective: The objective of the study was to compare intensity modulated radiotherapy (IMRT) and intensity modulated proton therapy (IMPT) for locally advanced cervical cancer in terms of dose-volume parameters, dose coverage and conformity. Furthermore, to study the effect of reduced margins. Materials and Methods: External beam radiotherapy planning of the pelvic region was carried out for 5 patients with locally advanced cervical cancer. Planning target volume (PTV) was defined by primary tumour, pelvic and regional lymph nodes. Dose prescription was 50.4 Gy in 28 fractions. PTV dose coverage criteria was set to D98% 95%. Two sets of treatment plans were prepared based on different CTV-PTV margins: clinical margin ( 7 mm L-R, 10 mm S-I, 15 mm A-P) and reduced margin (7 mm isotropic). The IMRT and IMPT plans were generated using the Eclipse treatment planning system. Dose-volume histograms (DVHs) were analyzed for the PTV and various organs at risk (OARs; rectum, bladder, bowel, sigmoideum and pelvic bone). Student’s t-test was used for all statistical comparison. Results: All IMRT and IMPT plans covered 98% of PTV with 95% isodose, so the dose prescription was well achieved. IMPT demonstrated the potential in sparing doses to OARs, where significant differences were seen compared to IMRT for many dose-volume parameters (table 1). Concerning the reduced margins, increased differences between IMPT and IMRT were seen for the bladder (data not shown). However, for the high dose regions in bowel and sigmoideum the potential sparing by IMPT was found to be less with reduced margins.

PO-0879: Short-course PET based SIB for cervical cancer

Purpose/Objective: State of the art treatment of locally advanced cervical cancer with image guided intensity modulated external radiotherapy followed by image guided brachytherapy provide good clinical outcome. However, there are still 10-15% loco-regional failures and 10-20% who experience moderate to severe side effects. In the current work we propose to use FDG PET as basis for a short-course simultaneous integrated boost (SIB) with external beam therapy. This concept may increase tumour control and improve tumour shrinkage before brachytherapy. The latter may reduce complexity and improve organ sparing at brachytherapy. Materials and Methods: This study included 10 patients with locally advanced cervical cancer all treated with curative image guided external beam and brachytherapy. FDG PET/CT was obtained prior to therapy for all patients. To explore the potential use of PET based dose escalation, a new approach was tested in silico. Here, the FDG avid tumour volume was dose escalated by intensity modulated radiotherapy from the conventional 1.8Gy to 2.8Gy per fraction for the 10 first fractions; a short-course SIB. For the remaining 18 external beam fractions, standard treatment to the pelvic area is followed to a total dose to the PTV and boost volume of 50.4Gy and 60.4Gy, respectively. For intensity modulation, both photons and protons were considered using dual arc VMAT and three-field IMPT, respectively. All treatment plans were generated using the Eclipse Treatment Planning System (v.11, Varian Medical Systems, Palo Alto, CA). Results: For the patients included, the PET based boost volume had a mean volume of 36 ± 6cm as compared to average volumes for the GTV and PTV of 69 ± 10cm and 1508 ± 55cm, respectively. The dose escalation was straightforward to implement for both VMAT and IMPT, with a D98 ≥ 95% for the boost volume being achieved in all cases. The sum of the short-course SIB (10 fractions) and the subsequent 18 conventional fractions was compared to the conventional, 28-fraction non-SIB approach by analysing dose volume histograms (Table 1). Only marginal increased doses to the relevant organs at risk (OARs) were found for all investigated parameters. IMPT had, compared to VMAT, reduced OAR doses in the intermediate dose range, but showed no relative advantage in dose escalation.