EVALUATION OF OXYGENATION STATUS DURING FRACTIONATED RADIOTHERAPY IN HUMAN NONSMALL CELL LUNG CANCERS USING [F-18] FLUOROMISONIDAZOLE POSITRON EMISSION TOMOGRAPHY

Purpose: Recent clinical investigations have shown a strong correlatio n between pretreatment tumor hypoxia and poor response to radiotherapy . These observations raise questions about standard assumptions of tum or reoxygenation during radiotherapy, which has been poorly studied in human cancers. Positron emission tomography (PET) imaging of [F-18]fl uoromisonidazole (FMISO) uptake allows noninvasive assessment of tumor hypoxia, and is amenable for repeated studies during fractionated rad iotherapy to systematically evaluate changes in tumor oxygenation. Met hods and Materials: Seven patients with locally advanced nonsmall cell lung cancers underwent sequential [F-18]FMISO PET imaging while recei ving primary radiotherapy. Computed tomograms were used to calculate t umor volumes, define tumor extent for PET image analysis, and assist i n PET image registration between serial studies. Fractional hypoxic vo lume (FHV) was calculated for each study as the percentage of pixels w ithin the analyzed imaged tumor volume with a tumor:blood [F-18]FMISO ratio greater than or equal to 1.4 by 120 min after injection. Serial FHVs were compared for each patient. Results: Pretreatment FHVs ranged from 20-84% (median 58%). Subsequent FHVs varied from 8-79% (median 2 9%) at midtreatment, and ranged from 3-65% (median 22%) by the end of radiotherapy. One patient had essentially no detectable residual tumor hypoxia by the end of radiation, while two others showed no apparent decrease in serial FHVs. There was no correlation between tumor size a nd pretreatment FHV. Conclusions: Although there is a general tendency toward improved oxygenation in human tumors during fractionated radio therapy, these changes are unpredictable and may be insufficient in ex tent and timing to overcome the negative effects of existing pretreatm ent hypoxia. Selection of patients for clinical trials addressing radi oresistant hypoxic cancers can be appropriately achieved through singl e pretreatment evaluations of tumor hypoxia tTumor hypoxia.