Tumor control probability for selective boosting of hypoxic subvolumes, including the effect of reoxygenation.

PURPOSE To study the effect on tumor control probability of selectively boosting the dose to hypoxic subvolumes. METHODS AND MATERIALS A Monte Carlo model was developed that separates the tumor into two compartments, one of which receives a primary dose, and one of which receives a higher boost dose. During radiation delivery, each compartment consists of three clonogen subpopulations: those that are well oxygenated, those that are temporarily hypoxic (geometrically transient hypoxia), and those that are permanently hypoxic (geometrically stable hypoxia). The spatial location of temporary hypoxia within the tumor volume varies over time, whereas, the spatial location of permanent hypoxia does not. The effect of reoxygenation was included. Clonogen proliferation was not included in the model. RESULTS A modest boost dose (120%-150% of the primary dose) increases tumor control probability to that found in the absence of permanent hypoxia. The entire hypoxic subvolume need not be included to obtain a significant benefit. However, only tumors with a geometrically stable hypoxic volume will have an improved control rate. CONCLUSIONS Tumors with an identifiable geometrically stable hypoxic volume will have an improved control rate if the dose to the hypoxic volume is escalated. Further work is required to determine the spatiotemporal evolution of the hypoxic volumes before and during the course of radiotherapy.

[1]  J.Martin Brown Tumor radiosensitivity: it's the subpopulations that count. , 2000, International journal of radiation oncology, biology, physics.

[2]  L. Golberg,et al.  Non-invasive assessment of human tumour hypoxia with 123I-iodoazomycin arabinoside: preliminary report of a clinical study. , 1992, British Journal of Cancer.

[3]  E. Hall,et al.  Radiobiology for the radiologist , 1973 .

[4]  J. Rosenman Incorporating functional imaging information into radiation treatment. , 2001, Seminars in radiation oncology.

[5]  V. Oikonen,et al.  Imaging of blood flow and hypoxia in head and neck cancer: initial evaluation with [(15)O]H(2)O and [(18)F]fluoroerythronitroimidazole PET. , 2001, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[6]  S Mutic,et al.  A novel approach to overcome hypoxic tumor resistance: Cu-ATSM-guided intensity-modulated radiation therapy. , 2001, International journal of radiation oncology, biology, physics.

[7]  P. Carroll,et al.  Three-dimensional H-1 MR spectroscopic imaging of the in situ human prostate with high (0.24-0.7-cm3) spatial resolution. , 1996, Radiology.

[8]  J. Moore,et al.  Radiation response and cure rate of human colon adenocarcinoma spheroids of different size: the significance of hypoxia on tumor control modelling. , 2001, International journal of radiation oncology, biology, physics.

[9]  J. Overgaard,et al.  Modification of Hypoxia-Induced Radioresistance in Tumors by the Use of Oxygen and Sensitizers. , 1996, Seminars in radiation oncology.

[10]  Y. Fujibayashi,et al.  Tumor uptake of copper-diacetyl-bis(N(4)-methylthiosemicarbazone): effect of changes in tissue oxygenation. , 2001, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[11]  P. Okunieff,et al.  Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. , 1989, Cancer research.

[12]  J H Hendry,et al.  A realistic closed-form radiobiological model of clinical tumor-control data incorporating intertumor heterogeneity. , 1998, International journal of radiation oncology, biology, physics.

[13]  J. Fowler,et al.  Selective boosting of tumor subvolumes. , 2000, International journal of radiation oncology, biology, physics.

[14]  P. Lambin,et al.  Oxygenation of head and neck tumors , 1993, Cancer.

[15]  A. Brahme,et al.  Optimal dose distribution for eradication of heterogeneous tumours. , 1987, Acta oncologica.

[16]  T K Lewellen,et al.  Quantifying regional hypoxia in human tumors with positron emission tomography of [18F]fluoromisonidazole: a pretherapy study of 37 patients. , 1996, International journal of radiation oncology, biology, physics.

[17]  C C Ling,et al.  Towards multidimensional radiotherapy (MD-CRT): biological imaging and biological conformality. , 2000, International journal of radiation oncology, biology, physics.

[18]  M Goitein,et al.  Causes and consequences of inhomogeneous dose distributions in radiation therapy. , 1986, International journal of radiation oncology, biology, physics.

[19]  T W Griffin,et al.  Imaging of hypoxia in human tumors with [F-18]fluoromisonidazole. , 1992, International journal of radiation oncology, biology, physics.

[20]  M Goitein,et al.  Implementation of a model for estimating tumor control probability for an inhomogeneously irradiated tumor. , 1993, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[21]  S Webb,et al.  A model for calculating tumour control probability in radiotherapy including the effects of inhomogeneous distributions of dose and clonogenic cell density. , 1993, Physics in medicine and biology.

[22]  P Vaupel,et al.  Oxygen status of malignant tumors: pathogenesis of hypoxia and significance for tumor therapy. , 2001, Seminars in oncology.

[23]  P. Vaupel,et al.  Hypoxia and Radiation Response in Human Tumors. , 1996, Seminars in radiation oncology.

[24]  B. Fertil,et al.  Distribution of radiation sensitivities for human tumor cells of specific histological types: comparison of in vitro to in vivo data. , 1986, International journal of radiation oncology, biology, physics.

[25]  C. Ling,et al.  Developments in nuclear magnetic resonance imaging and spectroscopy: application to radiation oncology. , 2001, Seminars in radiation oncology.

[26]  C. Ling,et al.  On measuring hypoxia in individual tumors with radiolabeled agents. , 2001, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.