Monitoring bone marrow proliferative activity with FLT during chemoradiation therapy of pelvic cancers

Objectives To monitor the proliferative activity of bone marrow within and outside of the radiation field (RT) with serial FLT imaging during chemoradiation therapy of pelvic cancers.

Methods Subjects (N=19) with pelvic cancer (6 rectal, 5 anal, 6 cervical, 1 vaginal, 1 bladder) scheduled to be treated with radio- and chemotherapy (3 capecitibine, 6 mitomycin/5FU, 3 5FU, 7 cisplatin) were serially imaged with [¹⁸F]fluorothymidine (FLT) at baseline, 1 week, 2 weeks and at 30 days post-end of therapy. Spinal marrow VOIs were defined in the sacrum, lumbar and thoracic spine by using a 50% maximum pixel value threshold on the baseline images. Subsequent images were co-registered to the baseline images (PFUSION PMOD) and the same VOIs were applied to measure changes from baseline. Results were scaled in SUV units at 60 minutes post-injection.

Results FLT uptake in marrow within the RT field (sacrum) decreased 78%±6% at wk 1 and 82%±7% at wk 2 (MANOVA p<0.0001), consistent with our previous findings in head & neck cancer (-76% at 1 wk, Menda, et al., 2010). At 30 d post-therapy, marrow uptake was recovering in all but 2 subjects (N=12, mean=-60%±17%). For marrow outside of the RT field (thoracic marrow), there were no significant changes in FLT uptake (MANOVA p=0.9), however, 12/16 and 11/15 for weeks 1 and 2, respectively, had increases from 2 to 47% whereas the balance of subjects had decrements from 11 to 47%. At 30 d post-therapy, the marrow FLT uptake was significantly increased (p<0.01) with a mean increase of 15% (range: -5% to 42%). 5FU therapy did not appear to influence the changes in FLT uptake except for less recovery in the RT field.

Conclusions Pelvic chemoradiation significantly altered the whole-body marrow uptake of FLT. Marrow in the radiation field experienced significant reductions that were tending to reverse by 30 d post-therapy. Marrow outside of the radiation field, in most subjects, maintained or increased FLT uptake even with exposure to chemotherapy.

Research Support R01 CA169336-02 (McGuire, PI)