Brigid McDonald^{1}, Renjie He^{1}, Yao Ding^{2}, Travis Salzillo^{2}, Jihong Wang^{2}, Clifton Fuller^{2}, and Abdallah Mohamed^{2}

^{1}Radiation Oncology, UT MD Anderson Cancer Center, Houston, TX, United States, ^{2}UT MD Anderson Cancer Center, Houston, TX, United States

### Synopsis

In
this study, we investigate weekly changes in mean and median apparent diffusion
coefficient (ADC) values from diffusion-weighted MRI for HPV+ oropharyngeal
cancer patients undergoing definitive radiation therapy (RT). Trends of
increasing ADC values in GTV_P and GTV_N were observed with clear separation at
each time point between patients with no evidence of disease vs. recurrence at
2 months post-RT. Because of our small sample size (15), a larger cohort is
needed for more robust outcome prediction analysis.

### Introduction

Diffusion-weighted magnetic resonance imaging (DW-MRI) is a
quantitative MRI technique that measures the diffusion of water throughout a
tissue. Its associated quantitative imaging biomarker, the apparent diffusion
coefficient (ADC), has been shown in recent studies as a potential imaging biomarker
for predicting response to radiation therapy (RT) in head and neck cancers.
However, most studies have only looked at differences between pre-RT and a single
mid-RT time point, leaving the overall ADC kinetics unknown. In this study, we
analyze weekly DW-MRI images throughout RT for human papillomavirus-positive
(HPV+) oropharyngeal cancer patients and investigate ADC and volumetric changes
in both primary tumors and lymph nodes.### Methods

15 HPV+ oropharyngeal cancer patients treated with definitive RT (70 Gy;
33 fractions) were included in this study (clinical demographics in Table 1).
All patients provided written informed consent to participate in this IRB-approved
study (NCT03224000; institutional IRB identifier: 2015-0851). Patients were
imaged at baseline and weekly during RT on a 1.5T MR-sim (Siemens Aera) with
fat-suppressed T2-weighted turbo spin echo and DW-MRI (12 imaged with BLADE, 3
with RESOLVE).
Sequence parameters (TR/TE (ms); pixel size/slice thickness (mm); b-values
(s/mm2)): T2-weighted (5280/80; 0.5/2; N/A), BLADE (5900/50; 2/4; 0 & 800),
RESOLVE (9380/63; 2/4; 0 & 800). A total of 15 primary gross tumor volumes (GTV_P) and 14 nodal gross tumor
volumes (GTV_N) were analyzed (14 nodes across 12 patients). The number of
structures omitted from analysis due to missing images, artifacts, or complete
response (CR) of a structure were 0, 2, 0, 1, 4, 4, 12 for baseline and weeks
1-6, respectively, for GTV_P and 0, 2, 1, 1, 0, 2, 6 for GTV_N. Differences
in mean and median ADC values between BLADE and RESOLVE were assessed at each
time point with the Kolmogorov–Smirnov test (α=0.05
for all statistical tests). The Kruskal-Wallis test was performed to detect
significant changes across all time points for mean and median ADC and volume
for GTV_P and GTV_N. Percent changes (%Δ) from baseline were calculated for the
same quantities. To test whether any of the studied quantities (weekly absolute
values and %Δ values) could predict response at 2-months post-RT, the Mann-Whitney
test was performed for the quantities at each week. The relationship between %Δvolume
and %ΔADC (mean and median) was assessed for each week using linear regression
and Spearman’s correlation.### Results

Mean
and median ADC values for BLADE vs. RESOLVE were not significantly different at
any time point except baseline (p=0.0285 for mean, p=0.0171 for median). Kruskal-Wallis
analysis revealed significant differences across time points for GTV_P mean
(p<0.0001), median (p<0.0001), and volume (p<0.0001) and GTV_N median
(p=0.0439) but no significant difference for GTV_N mean (p=0.0534) and volume
(p=0.1161). None of the studied parameters (mean, median, volume, and %Δ values)
showed a significant difference between responders and non-responders at
2-months post-RT. However, visual inspection of the data (Figure 1) showed higher
overall mean and median ADC for responders compared to non-responders for both GTV_P
and GTV_N. Responders also showed higher overall GTV_P volumes but lower
overall GTV_N volumes compared to non-responders. %Δmean and %Δvolume kinetics for
individual patients are shown in Figure 2. Linear correlations were nonexistent
or very weak for %Δvolume vs. %Δmean and %Δvolume vs. %Δmedian
at each week for GTV_P and GTV_N (maximum r2=0.36). None of the
pairs had a significant Spearman correlation except GTV_N week 3 %Δvolume vs. %Δmean
(p=0.0438) and vs. %Δmedian (0.0325).### Discussion

Our data supports trends seen in the literature that ADC values
increase as a tumor responds to RT due to the RT-induced breakdown of cellular
membranes. Although Figure 1 shows consistently higher ADC values at each time
point for responders compared to non-responders, these differences were not significantly
different in the Mann-Whitney test, which is most likely due to the small
sample size and low number of recurrence events (2 patients/3 lymph nodes).
This patient population was all HPV+ oropharyngeal cancer (and all but one were
early stage), which generally has a favorable response to RT, so a larger
cohort is needed for further analysis. Another limitation of this study is that
two DW-MRI sequences were used due to an unforeseen change in scan protocols
during the course of this study. The Kolmogorov–Smirnov test showed that differences
between the two sequences were not significant at any time point except one,
but further analysis with these sequences taken on the same patients should be
pursued to reliably quantify any major differences or overall ADC bias between
the sequences.### Conclusion

Trends of increasing ADC values in GTV_P and GTV_N were observed for
our cohort of 15 HPV+ oropharyngeal cancer patients. However, a larger cohort
is needed for more robust outcome prediction analysis.### Acknowledgements

No acknowledgement found.### References

No reference found.