title: 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.
authors.affiliation: Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo, Norway. eirik.malinen@fys.uio.no
authors.forename: Eirik
authors.initials: E
authors.lastname: Malinen
authors.forename: Aste
authors.initials: A
authors.lastname: Søvik
authors.forename: Dimitre
authors.initials: D
authors.lastname: Hristov
authors.forename: Øyvind S
authors.initials: ØS
authors.lastname: Bruland
authors.forename: Dag Rune
authors.initials: DR
authors.lastname: Olsen
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000494:pharmacology; D004285:Dogs; D006801:Humans; D000860:Hypoxia; D009369:Neoplasms / Q000532:radiotherapy*; D009669:Nose Neoplasms / Q000532:radiotherapy; D011336:Probability; D011878:Radiotherapy / Q000379:methods*; D011880:Radiotherapy Planning, Computer-Assisted; D020266:Radiotherapy, Conformal / Q000379:methods; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D012509:Sarcoma / Q000532:radiotherapy; D013997:Time Factors
chemical_list: D003287:Contrast Media