Clinical Investigation
Changes in Cervical Cancer FDG Uptake During Chemoradiation and Association With Response

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Purpose

Previous research showed that pretreatment uptake of F-18 fluorodeoxyglucose (FDG), as assessed by the maximal standardized uptake value (SUVmax) and the variability of uptake (FDGhetero), predicted for posttreatment response in cervical cancer. In this pilot study, we evaluated the changes in SUVmax and FDGhetero during concurrent chemoradiation for cervical cancer and their association with post-treatment response.

Methods and Materials

Twenty-five patients with stage Ib1-IVa cervical cancer were enrolled. SUVmax, FDGhetero, and metabolic tumor volume (MTV) were recorded from FDG-positron emission tomography (PET)/computed tomography (CT) scans performed pretreatment and during weeks 2 and 4 of treatment and were evaluated for changes and association with response assessed on 3-month post-treatment FDG-PET/CT.

Results

For all patients, the average pretreatment SUVmax was 17.8, MTV was 55.4 cm3, and FDGhetero was −1.33. A similar decline in SUVmax was seen at week 2 compared with baseline and week 4 compared with week 2 (34%). The areas of highest FDG uptake in the tumor remained relatively consistent on serial scans. Mean FDGhetero decreased during treatment. For all patients, MTV decreased more from week 2 to week 4 than from pretreatment to week 2. By week 4, the average SUVmax had decreased by 57% and the MTV had decreased by 30%. Five patients showed persistent or new disease on 3-month post-treatment PET. These poor responders showed a higher average SUVmax, larger MTV, and greater heterogeneity at all 3 times. Week 4 SUVmax (P=.037), week 4 FDGhetero (P=.005), pretreatment MTV (P=.008), and pretreatment FDGhetero (P=.008) were all significantly associated with post-treatment PET response.

Conclusions

SUVmax shows a consistent rate of decline during treatment and declines at a faster rate than MTV regresses. Based on this pilot study, pretreatment and week 4 of treatment represent the best time points for prediction of response.

Introduction

Approximately 20%-40% of patients with locally advanced cervical cancer treated with definitive chemoradiation will have persistent or recurrent disease after treatment 1, 2. Being able to identify those patients at high risk for a poor response to conventional therapy before or during treatment could lead to improved outcomes through modification of the treatment plan or use of adjuvant therapy.

Previous studies identified 3 different positron emission tomography with F-18 fluorodeoxyglucose (FDG-PET)-based prognostic factors for intact cervical cancer being treated definitively with concurrent chemoradiation. Specifically, high FDG uptake in the primary cervical tumor, measured as the maximum standardized uptake value (SUVmax) predicted for lymph node involvement, treatment response, recurrence risk, and overall survival (3). Similarly, the degree of variability of FDG uptake (FDGhetero) across a primary cervical tumor predicted for lymph node involvement, treatment response, local recurrence, and progression-free survival (4). Earlier research also found that primary cervical metabolic tumor volume (MTV) assessed on FDG-PET is associated with progression-free and overall survival (5).

Based on these studies, a prospective pilot study was initiated to evaluate how SUVmax, FDGhetero, and MTV changed during chemoradiation, using week 2 and week 4 during-treatment PET, and analyzing how these changes correlated with response on 3-month post-therapy PET, as other research showed that response assessment at this time predicted long-term outcome and survival (6).

Section snippets

Patients

This prospective cohort study included 25 patients with newly diagnosed International Federation of Obstetrics and Gynecology stage Ib1-IVa cervical cancer who were treated definitively with concurrent cisplatin and radiation. The study was approved by the Human Research Protection Office (HRPO 08-0804). Written informed consent was obtained from all patients.

All patients were treated with a combination of external beam radiation therapy (EBRT), high-dose-rate (HDR) intracavitary brachytherapy,

Patient characteristics

Twenty-five patients enrolled on the study between September 2008 and October 2010. Initial patient characteristics are included in Table 1. The average pretreatment PET characteristics were: primary cervix tumor SUVmax was 17.8 (range, 6.2-32.3), FDGhetero was −1.33 (range, −6.2 to −0.16), and MTV 55.4 cm3 (range, 7.6-251.1 cm3).

During-treatment FDG-PET changes

Figure 1 shows examples of the changes in primary cervical tumor FDG uptake during the course of therapy; qualitatively, we noted that the areas of highest FDG uptake

Discussion

Performing FDG-PET during treatment offers a unique opportunity to assess response to therapy before the completion of treatment, which could allow for modifications to improve the long-term outcome for patients. During-treatment imaging was initially applied for chemotherapy treatment assessment 7, 8. More recently, various groups have assessed during-treatment PET response with radiation or chemoradiation for cancers of the lung, rectum, and other sites 9, 10, 11, 12, 13, 14. Although

Conclusion

With 20%-40% of cervical cancer patients treated with concurrent chemoradiation experiencing recurrent or persistent disease 1, 2, being able to identify these high-risk patients in order to provide treatment intensification could have significant benefits. The present study confirms the prognostic value of pretreatment PET-based factors and identifies week 4 of treatment as another valuable time point for providing an early assessment of response, specifically with week 4 SUVmax and FDGhetero

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Conflict of interest: none.

Funding provided by RO1 CA136931 and 2008 RSNA Resident Research Grant #RR00807.

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