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Hypoxia-Guided Therapy for Head and Neck Cancers
PracticeUpdate: In relation to new remedies being tried, could you share some insight on work being undertaken regarding hypoxia-guided therapy for head and neck cancers?
Dr. Burtness: In thinking about whether or not hypoxia characterization can be used to guide treatment de-intensification in head and neck cancer, I think it's important to understand a little bit about the differences in hypoxia and in radiosensitivity between those patients who have HPV-associated head and neck cancer and those who do not. Firstly, hypoxia is more common and more extensive in bulkier HPV-negative disease. But we do now know from functional imaging studies, that there is hypoxia in HPV-associated disease as well, and this has been confirmed by tissue studies. Nancy Lee at Memorial Sloan Kettering and her group undertook a trial of adaptive radiation de-intensification guided by hypoxia imaging.
They started with a cohort of 19 patients, and this was reported in the Journal of the National Cancer Institute, where everybody had FMISO imaging to look at their hypoxic state. Everybody began the radiation, and then towards the conclusion of 30 Gy, they had another imaging study to assess their hypoxia. If the hypoxia had resolved or if they never had any hypoxia to begin with, their radiation for HPV-associated disease was just 30 Gy. Because this was the very first test of this, they did take all of those patients to biopsy and neck dissection. For that first cohort of 19 patients, it wasn't really a treatment de-intensification, but they found very high pathologic complete response rate in those patients who had baseline hypoxia. They have now gone forward with a large trial, looking at treatment de-intensification for patients who were either hypoxic, have no hypoxia at baseline, or are hypoxic at baseline, but the hypoxia resolves, with the anticipation that the no hypoxia baseline group is going to be the most favorable.
PracticeUpdate: What all factors make the hypoxia-guided therapy favorable in head and neck cancers?
Dr. Burtness: I think one of the things that makes this possible is the extraordinary responsiveness of HPV-associated disease to radiation, and this has been hypothesized to be related to the presence of wild-type p53 or the somewhat lesser degree of hypoxia, the somewhat less complicated mutational status. Very recently, work from MD Anderson has indicated that there's much greater sensitivity to DNA damage because of the effects of the viral oncogene E7 on Rb and the downstream effects of that on replication, stress, and homologous recombination. I think that there's still a lot to be learned about how we could best exploit this radiosensitivity and how we could best exploit the nature of the molecular abnormalities in HPV-associated head and neck cancer to some doses of radiation. I think at present these are very much clinical trials questions and should not be guiding therapy in everyday practice.
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