Adapting radiotherapy to hypoxic tumours

Abstract

In the current work, the concepts of biologically adapted radiotherapy of hypoxic tumours in a framework encompassing functional tumour imaging, tumour control predictions, inverse treatment planning and intensity modulated radiotherapy (IMRT) were presented. Dynamic contrast enhanced magnetic resonance imaging (DCEMRI) of a spontaneous sarcoma in the nasal region of a dog was employed. The tracer concentration in the tumour was assumed related to the oxygen tension and compared to Eppendorf histograph measurements. Based on the pO(2)-related images derived from the MR analysis, the tumour was divided into four compartments by a segmentation procedure. DICOM structure sets for IMRT planning could be derived thereof. In order to display the possible advantages of non-uniform tumour doses, dose redistribution among the four tumour compartments was introduced. The dose redistribution was constrained by keeping the average dose to the tumour equal to a conventional target dose. The compartmental doses yielding optimum tumour control probability (TCP) were used as input in an inverse planning system, where the planning basis was the pO(2)-related tumour images from the MR analysis. Uniform (conventional) and non-uniform IMRT plans were scored both physically and biologically. The consequences of random and systematic errors in the compartmental images were evaluated. The normalized frequency distributions of the tracer concentration and the pO(2) Eppendorf measurements were not significantly different. 28% of the tumour had, according to the MR analysis, pO(2) values of less than 5 mm Hg. The optimum TCP following a non-uniform dose prescription was about four times higher than that following a uniform dose prescription. The non-uniform IMRT dose distribution resulting from the inverse planning gave a three times higher TCP than that of the uniform distribution. The TCP and the dose-based plan quality depended on IMRT parameters defined in the inverse planning procedure (fields and step-and-shoot intensity levels). Simulated random and systematic errors in the pO(2)-related images reduced the TCP for the non-uniform dose prescription. In conclusion, improved tumour control of hypoxic tumours by dose redistribution may be expected following hypoxia imaging, tumour control predictions, inverse treatment planning and IMRT.

Dose prescription complexity versus tumor control probability in biologically conformal radiotherapy

“…In order to allow a fair quantitative comparison between plans of differing complexity, we used a method which maximizes the TCP by redistributing dose between compartments, subject to a fixed integral dose 8,16,20 . This method has been previously described by the authors 15 .…”

“…With information on biological variations within a tumor, obtained using functional imaging, it is possible to individualize the dose prescription to each imaged voxel within 50 the target 8,12,14,15 . However, more commonly the target has been divided into a small number of compartments such that the quasi-continuous optimal dose distribution is quantized into a few discrete dose levels [5][6][7]9,16 . The aim of this work is to investigate the relationship between the complexity of a treatment prescription, measured by the number of prescribed dose levels, and the quality of the plan, represented by the TCP.…”

Fluorine-18-Labeled Fluoromisonidazole Positron Emission and Computed Tomography-Guided Intensity-Modulated Radiotherapy for Head and Neck Cancer: A Feasibility Study

“…One could dose escalate the entire GTV; however, an indiscriminate increase in the dose to the GTV could deliver unnecessary radiation to the normal tissues found within or around the GTV, possibly at the expense of increasing the incidence of late complications. An alternative method is to differentially dose escalate within the GTV (37)(38)(39)(40)(41). Because IMRT has the ability to dose paint different regions within the target, one can use this technology to selectively deliver an increased dose to the GTV h if the intratumor location can be identified.…”

Dynamic contrast enhanced magnetic resonance imaging of bladder cancer and implications for biological image-adapted radiotherapy

“…Using the root mean square deviation (RMSD) to evaluate the simulated delivery, a clear reduction in the patient averaged RMSD when using dose cubes of 2.5 mm compared to cubes of 5 and 10 mm was found ( Figure 5). In a previous study, where nonuniform tumor dose distributions using IMRT with 2.5 mm multi-leaf collimators were investigated [5], RMSD and the estimated tumor control probability (TCP) were highly correlated quantities. Thus, RMSD appears to be a suitable metric for evaluating the quality of adapted treatments.…”