Visualization and quantification of tumour biology for personalized radiotherapy

There are many types of cancer and there are significant differences between patients, between tumours, and even within a single tumour. These differences make cancer a difficult disease to cure and tend to result in different treatment outcomes. Functional imaging is a minimally invasive method of examining tumour biology in 3D. This dissertation used functional imaging techniques to classify the tumour and examine tumour sub-volumes. The absorption of a labelled drug, tumour circulation, tumour metabolism and tumour oxygen deficiency were measured and tested as markers to determine patient prognoses, to predict the treatment outcome and to adjust radiotherapy treatment plans

Impact of SBRT fractionation in hypoxia dose painting - Accounting for heterogeneous and dynamic tumor oxygenation

Purpose Tumor hypoxia, often found in nonsmall cell lung cancer (NSCLC), implies an increased resistance to radiotherapy. Pretreatment assessment of tumor oxygenation is, therefore, warranted in these patients, as functional imaging of hypoxia could be used as a basis for dose painting. This study aimed at investigating the feasibility of using a method for calculating the dose required in hypoxic subvolumes segmented on F-18-HX4 positron emission tomography (PET) imaging of NSCLC. Methods Positron emission tomography imaging data based on the hypoxia tracer F-18-HX4 of 19 NSCLC patients were included in the study. Normalized tracer uptake was converted to oxygen partial pressure (pO(2)) and hypoxic target volumes (HTVs) were segmented using a threshold of 10 mmHg. Uniform doses required to overcome the hypoxic resistance in the target volumes were calculated based on a previously proposed method taking into account the effect of interfraction reoxygenation, for fractionation schedules ranging from extremely hypofractionated stereotactic body radiotherapy (SBRT) to conventionally fractionated radiotherapy. Results Gross target volumes ranged between 6.2 and 859.6 cm(3), and the hypoxic fraction <10 mmHg between 1.2% and 72.4%. The calculated doses for overcoming the resistance of cells in the HTVs were comparable to those currently prescribed in clinical practice as well as those previously tested in feasibility studies on dose escalation in NSCLC. Depending on the size of the HTV and the distribution of pO(2), HTV doses were calculated as 43.6-48.4 Gy for a three-fraction schedule, 51.7-57.6 Gy for five fractions, and 59.5-66.4 Gy for eight fractions. For patients in whom the HTV pO(2) distribution was more favorable, a lower dose was required despite a bigger volume. Tumor control probability was lower for single-fraction schedules, while higher levels of tumor control probability were found for schedules employing several fractions. Conclusions The method to account for heterogeneous and dynamic hypoxia in target volume segmentation and dose prescription based on F-18-HX4-PET imaging appears feasible in NSCLC patients. The distribution of oxygen partial pressure within HTV could impact the required prescribed dose more than the size of the volume

Фінансовий контролінг як інструмент управління діяльністю суб'єкта господарювання

PURPOSE: Multiple imaging techniques are nowadays available for clinical in-vivo visualization of tumour biology. FDG PET/CT identifies increased tumour metabolism, hypoxia PET visualizes tumour oxygenation and dynamic contrast-enhanced (DCE) CT characterizes vasculature and morphology. We explored the relationships among these biological features in patients with non-small-cell lung cancer (NSCLC) at both the patient level and the tumour subvolume level. METHODS: A group of 14 NSCLC patients from two ongoing clinical trials (NCT01024829 and NCT01210378) were scanned using FDG PET/CT, HX4 PET/CT and DCE CT prior to chemoradiotherapy. Standardized uptake values (SUV) in the primary tumour were calculated for the FDG and hypoxia HX4 PET/CT scans. For hypoxia imaging, the hypoxic volume, fraction and tumour-to-blood ratio (TBR) were also defined. Blood flow and blood volume were obtained from DCE CT imaging. A tumour subvolume analysis was used to quantify the spatial overlap between subvolumes. RESULTS: At the patient level, negative correlations were observed between blood flow and the hypoxia parameters (TBR >1.2): hypoxic volume (−0.65, p = 0.014), hypoxic fraction (−0.60, p = 0.025) and TBR (−0.56, p = 0.042). At the tumour subvolume level, hypoxic and metabolically active subvolumes showed an overlap of 53 ± 36 %. Overlap between hypoxic sub-volumes and those with high blood flow and blood volume was smaller: 15 ± 17 % and 28 ± 28 %, respectively. Half of the patients showed a spatial mismatch (overlap <5 %) between increased blood flow and hypoxia. CONCLUSION: The biological imaging features defined in NSCLC tumours showed large interpatient and intratumour variability. There was overlap between hypoxic and metabolically active subvolumes in the majority of tumours, there was spatial mismatch between regions with high blood flow and those with increased hypoxia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00259-015-3169-4) contains supplementary material, which is available to authorized users

Nitroglycerin as a radiosensitizer in non-small cell lung cancer: Results of a prospective imaging-based phase II trial

Background: Nitroglycerin is proposed as an agent to reduce tumour hypoxia by improving tumour perfusion. We investigated the potent

High-dose-rate prostate brachytherapy based on registered transrectal ultrasound and in-room cone-beam CT images

Purpose\ud To present a high-dose-rate (HDR) brachytherapy procedure for prostate cancer using transrectal ultrasound (TRUS) to contour the regions of interest and registered in-room cone-beam CT (CBCT) images for needle reconstruction. To characterize the registration uncertainties between the two imaging modalities and explore the possibility of performing the procedure solely on TRUS.\ud \ud Methods and Materials\ud Patients were treated with a TRUS/CBCT-based HDR brachytherapy procedure. For 100 patients, dosimetric results were analyzed. For 40 patients, registration uncertainties were examined by determining differences in fiducial marker positions on TRUS and registered CBCT. The accuracy of needle reconstruction on TRUS was investigated by determining the position differences of needle tips on TRUS and CBCT. The dosimetric impact of reregistration and needle reconstruction on TRUS only was studied for 8 patients.\ud \ud Results\ud The average prostate V100 was 97.8%, urethra D10 was 116.3%, and rectum D1 cc was 66.4% of the prescribed dose. For 85% of the patients, registration inaccuracies were within 3 mm. Large differences were found between needle tips on TRUS and CBCT, especially in cranial–caudal direction, with a maximum of 10.4 mm. Reregistration resulted in a maximum V100 reduction of 0.9%, whereas needle reconstruction on TRUS only gave a maximum reduction of 9.4%.\ud \ud Conclusions\ud HDR prostate brachytherapy based on TRUS combined with CBCT is an accurate method. Registration uncertainties, and consequently dosimetric inaccuracies, are small compared with the uncertainties of performing the procedure solely based on static TRUS images. CBCT imaging is a requisite in our current procedure

Non-invasive imaging prediction of tumor hypoxia: A novel developed and externally validated CT and FDG-PET-based radiomic signatures

Contains fulltext : 228714.pdf (Publisher’s version ) (Open Access

The impact of organ motion and the appliance of mitigation strategies on the effectiveness of hypoxia-guided proton therapy for non-small cell lung cancer

BACKGROUND AND PURPOSE: To investigate the impact of organ motion on hypoxia-guided proton therapy treatments for non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: Hypoxia PET and 4D imaging data of six NSCLC patients were used to simulate hypoxia-guided proton therapy with different motion mitigation strategies including rescanning, breath-hold, respiratory gating and tumour tracking. Motion-induced dose degradation was estimated for treatment plans with dose painting of hypoxic tumour sub-volumes at escalated dose levels. Tumour control probability (TCP) and dosimetry indices were assessed to weigh the clinical benefit of dose escalation and motion mitigation. In addition, the difference in normal tissue complication probability (NTCP) between escalated proton and photon VMAT treatments has been assessed. RESULTS: Motion-induced dose degradation was found for target coverage (CTV V95% up to -4%) and quality of the dose-escalation-by-contour (QRMS up to 6%) as a function of motion amplitude and amount of dose escalation. The TCP benefit coming from dose escalation (+4-13%) outweighs the motion-induced losses (<2%). Significant average NTCP reductions of dose-escalated proton plans were found for lungs (-14%), oesophagus (-10%) and heart (-16%) compared to conventional VMAT plans. The best plan dosimetry was obtained with breath hold and respiratory gating with rescanning. CONCLUSION: NSCLC affected by hypoxia appears to be a prime target for proton therapy which, by dose-escalation, allows to mitigate hypoxia-induced radio-resistance despite the sensitivity to organ motion. Furthermore, substantial reduction in normal tissue toxicity can be expected compared to conventional VMAT. Accessibility and standardization of hypoxia imaging and clinical trials are necessary to confirm these findings in a clinical setting