Repeatability of hypoxia dose painting by numbers based on EF5-PET in head and neck cancer.

BACKGROUND: Hypoxia dose painting is a radiotherapy technique to increase the dose to hypoxic regions of the tumour. Still, the clinical effect relies on the reproducibility of the hypoxic region shown in the medical image. 18F-EF5 is a hypoxia tracer for positron emission tomography (PET), and this study investigated the repeatability of 18F-EF5-based dose painting by numbers (DPBN) in head and neck cancer (HNC). MATERIALS AND METHODS: Eight HNC patients undergoing two 18F-EF5-PET/CT sessions (A and B) before radiotherapy were included. A linear conversion of PET signal intensity to radiotherapy dose prescription was employed and DPBN treatment plans were created using the image basis acquired at each PET/CT session. Also, plan A was recalculated on the image basis for session B. Voxel-by-voxel Pearson's correlation and quality factor were calculated to assess the DPBN plan quality and repeatability. RESULTS: The mean (SD) correlation coefficient between DPBN prescription and plan was 0.92 (0.02) and 0.93 (0.02) for sessions A and B, respectively, with corresponding quality factors of 0.02 (0.002) and 0.02 (0.003), respectively. The mean correlation between dose prescriptions at day A and B was 0.72 (0.13), and 0.77 (0.12) for the corresponding plans. A mean correlation of 0.80 (0.08) was found between plan A, recalculated on image basis B, and plan B. CONCLUSION: Hypoxia DPBN planning based on 18F-EF5-PET/CT showed high repeatability. This illustrates that 18F-EF5-PET provides a robust target for dose painting.

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.

Short-course PET based simultaneous integrated boost for locally advanced cervical cancer.

BACKGROUND: Patients with large, locally advanced cervical cancers (LACC) are challenging to treat. The purpose of this work is to use 18F-FDG PET as planning basis for a short-course simultaneous integrated boost (SIB) in external beam radiotherapy of LACC in order to increase tumour shrinkage and likelihood of local control. METHODS: Ten previously treated patients with LACC were included, all with pre-treatment FDG PET/CT images available. The FDG avid tumour volume, MTV50, was dose escalated in silico by intensity modulated radiotherapy from the standard 1.8 Gy to 2.8 Gy per fraction for the 10 first fractions; a short-course SIB. For the 18 remaining external fractions, standard pelvic treatment followed to total PTV and MTV50 doses of 50.4 Gy and 60.4 Gy, respectively. Photon and proton treatment were considered using volumetric modulated arc treatment (VMAT) and intensity-modulated proton therapy (IMPT), respectively. All treatment plans were generated using the Eclipse Treatment Planning System (TPS). The impact of tumour shrinkage on doses to organs at risk (OARs) was simulated in the TPS for the SIB plans. RESULTS: Dose escalation could be implemented using both VMAT and IMPT, with a D98 ≥ 95 % for MTV50 being achieved in all cases. The sum of the 10 fraction short-course SIB and subsequent 18 standard fractions was compared to the standard non-SIB approach by dose volume histogram (DVH) analysis. Only marginal increase of dose to OARs was found for both modalities and a small further increase estimated from tumour shrinkage. Most DVH parameters showed a mean difference below 2 %. IMPT had, compared to VMAT, reduced OAR doses in the low to intermediate dose range, but showed no additional advantage in dose escalation. CONCLUSIONS: Planning of dose escalation based on a FDG avid boost volume was here demonstrated feasible. The concept may allow time for enhanced tumour shrinkage before brachytherapy. Thus, this strategy may prove clinically valuable, in particular for patients with large tumours.

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

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 (18)F-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.

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

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.