Tumor perfusion and hypoxia have been of significant interest among head and neck radiation oncologists and radiologists, as it has been shown in radiobiologic studies that tumor hypoxia is a major determinant of radiation resistance in patients undergoing curative-intent radiotherapy for head and neck cancer. In our study we sought to define tumor perfusion parameters—including blood flow, blood volume, capillary permeability surface product, and mean transit time in the primary tumor of patients with head and neck cancer during a course of radiotherapy—and to determine how these parameters change during the course of radiotherapy, as well as the potential to predict treatment outcome.  We found that pretreatment tumor blood flow was higher and increased to a greater extent during the second week of radiotherapy in patients achieving locoregional control compared with patients who failed radiotherapy. After radiotherapy, blood flow and blood volume parameters decreased in all patients, likely reflecting varying degrees of tumor response to therapy.

These findings have been corroborated in other institutional series, though there are variations in perfusion parameters between different institutional series, and this may reflect the heterogeneity of the lesions, the placement of measurement, or differences in dose delivery and time measurements. Tumor size and location may also affect perfusion measurements, such as in laryngeal tumors, where motion artifact can affect the results.

We have been contacted by a number of authors who understand the importance and potential implications of tumor perfusion imaging in head and neck cancer, and who have encouraged us to continue our work. We

have performed subsequent studies measuring perfusion of normal tissue in patients undergoing radiotherapy, and implications of normal tissue perfusion on acute and late toxicity of radiotherapy, including dysphagia and mucositis. These findings have also been published.^1,2 Some limitations include that CTP is user-dependent and relies on availability of the software and user interpretation, and, hence, is not yet widely adopted in standard clinical practice. Once standardization of software between vendors can be accomplished it may be possible to integrate this into prospective clinical trials. At this time, the CTP datasets are too large to be integrated into radiation therapy planning. However, theoretically, if the areas of decreased or increased perfusion representing differential levels of radiosensitivity can be determined, then radiation techniques such as intensity-modulated radiation therapy and adaptive radiotherapy techniques could preferentially target more resistant areas with dose painting techniques. Early prediction of response and long-term control after curative-intent radiotherapy is the Holy Grail in radiation oncology, as current imaging techniques require at least a 10-12 week period after completion of a course of radiotherapy before functional imaging such as PET/CT or clinical examination findings are performed to determine the outcome of treatment.

Other areas of research that have come from this initial study include investigating MR perfusion techniques in head and neck cancer, as this obviates the concern for low-dose radiation exposure from diagnostic CTP.

References

1. Truong MT, Lee R, Saito N, et al. Correlating computed tomography perfusion changes in the pharyngeal constrictor muscles during head-and-neck radiotherapy to dysphagia outcome. Int J Radiat Oncol Biol Phys 2012;82:e119-27. doi: 10.1016/j.ijrobp.2011.04.058. Epub 2011 Jun 12. PMID: 21669502
2. Saito N, Truong MT, Qureshi MM, et al. Correlation of mucositis during head and neck radiotherapy with CT perfusion imaging of the oropharyngeal mucosa. Accepted in J Comput Assist Tomogr on 10/3/2012.

 

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