Session Item

Hematological toxicity after chemoradiotherapy is partially caused by direct radiation to the highly radiosensitive bone marrow, but the dose-response and the potential compensatory effect in non-irradiated bone marrow remain to be better understood. For this purpose, FDG-PET allows assessment of the metabolic activity within the bone marrow and is correlated with higher cellularity and proliferative activity.
This study explored how bone marrow within individual vertebrae responds to radiotherapy for NSCLC patients, by measuring changes in FDG-PET uptake from baseline to end of radiotherapy and correlating with the dose to the individual vertebrae.

We identified and analyzed 15 NSCLC patients referred for radiotherapy with curative intent (66 Gy in 33 fractions) between Jan 2019-Dec 2019, all having an FDG-PET/CT before treatment and a follow-up PET/CT within 12 months.
Each vertebra was segmented and labeled (cervical (C1-7); thoracic (T1-12); and lumbar (L1-L5) vertebrae) using CT as input to the deep learning model winning MICCAI’s VerSe challenge 2019.
The FDG-PET mean standardized uptake values (SUV_mean) within each vertebra at baseline and follow-up were assessed and their relative differences were calculated with baseline as reference (ΔSUV_mean). The delivered mean dose (D_mean) to each vertebra was obtained from the dose plan. We used Spearman's correlation (ρ) to measure the association between the D_mean and ΔSUV_mean using data from all vertebrae across all patients. 

The SUV_mean for each vertebra at baseline and follow-up and the corresponding D_mean are shown for an illustrative patient in Fig 1. A drop in SUV_mean for vertebrae receiving high doses is seen together with a potentially compensating increased uptake for the vertebrae receiving only scatter dose.
Figure 1: SUV_mean of each vertebra at baseline and follow-up  (left y-axis) and the corresponding D_mean (right y-axis).

Across all vertebrae, there was a strong correlation between D_mean and ΔSUV_mean (ρ=-0.43, p-val<0.0001), with uptake decreasing with increasing dose. This can also be seen from Fig 2, showing a scatterplot of the D_mean and ΔSUV_mean and a rolling mean line to indicate the trend. There is a slightly increased SUV_mean at low D_mean, supporting the hypothesis of a compensatory response to radiation injury in the irradiated vertebrae. However, the individual out-of-field responses are mixed so a greater understanding is needed.

Figure 2: Scatterplot between and D_mean and ΔSUV_mean. Each point denotes a vertebra and the solid line indicates the rolling mean.

This study used longitudinal FDG-PET/CT scans as a unique method to demonstrate both a dose-response of the hematopoietic activity in bone marrow as well as a patient-dependent compensatory response in non-irradiated bone marrow. These results are the first step towards an in-depth evaluation of using FDG-PET to obtain a better understanding of the bone marrow’s dose-response, compensatory response, and hematological toxicity.