Temporal Changes in Tumor Perfusion Pattern during the Radiation Therapy Course and their Clinical Significance in Cervical Cancer

Article Outline

• Purpose/Objective(s)
• Materials/Methods
• Results
• Conclusions
• Copyright

Back to Article Outline

Purpose/Objective(s) 

Associations between tumor perfusion status assessed by dynamic-contrast-enhanced (DCE) MRI and tumor control have been reported. However, the temporal change of tumor perfusion during treatment and impact on treatment outcome has not been well defined. This study evaluated the temporal change of heterogeneous tumor perfusion patterns during treatment, and its influence on local tumor control and survival in cervical cancer.

Back to Article Outline

Materials/Methods 

Ninety-eight advanced cervical cancer patients (stages IB2-IVA) were treated with radiation therapy (RT)/chemotherapy. Serial DCE-MRI scans were performed at three well-defined time points before RT (pre-RT), early RT (at 20-25 Gy/2-2.5 weeks), and mid-RT (at 45-50 Gy/4-5 weeks). The time-signal intensity (SI) curve and the plateau SI were derived for each tumor pixel of each DCE MRI. The poorly perfused tumor subregions were quantified as lower 10th percentiles of SI among the tumor pixels (SI10). Outcome endpoints, local tumor control and disease-free survival, were correlated with perfusion parameters of the pre-RT, early RT, and mid-RT MRI. Median follow was 4.6 (range: 0.2-9.0) years.

Back to Article Outline

Results 

Patterns of DCE of the tumor pixels changed during treatment, and the change influenced therapy outcome: In the pre-RT MRI, 16 patients with initial high perfusion (SI10 ≥ 2.1) had excellent outcome (100% local control and 81% disease-free survival). In 28 (34%) of the 82 patients with initially low perfusion (SI10 < 2.1) on pre-RT MR, the pattern changed to high perfusion in early-RT (at 20-25 Gy). These patients had an improved local control rate of 93%, compared to those with persistently low perfusion in pre-RT and early-RT MRIs (72%, p = 0.014). If low perfusion persisted to the mid-RT phase (at 45-50 Gy), local control rate decreased further to 66% (p = 0.008). Patients with persistently low perfusion had a disease-free survival rate of 44%, compared to 81% in those with high pre-RT perfusion, and 72% in those with low pre-RT and subsequently high perfusion (p = 0.01). In patients with initially high perfusion pre-RT, a subsequent decrease in SI did not negatively impact on outcome.

Back to Article Outline

Conclusions 

Tumor perfusion pattern varies during treatment, and such changes critically influence treatment outcome. Persistently low perfusion from the pre-RT through mid-RT phase indicates high risk of treatment failure, while better outcome is associated with high initial, or high subsequent perfusion patterns, even with prior status of poor perfusion. Our limited data suggest that DCE MRI is an effective and non-invasive means to assess the temporal changes of tumor perfusion status during the treatment, which may play an essential role in tumor reoxygenation and radioresponsiveness.