Use of neoadjuvant chemotherapy prior to radical hysterectomy in cervical cancer: monitoring tumour shrinkage and molecular profile on magnetic resonance and assessment of 3-year outcome

Abstract

The objective of this study is to assess tumour response to neoadjuvant chemotherapy prior to radical hysterectomy in cervical cancer using magnetic resonance (MR) to monitor tumour volume and changes in molecular profile and to compare the survival to that of a control group. Eligibility included Stage Ib-IIb previously untreated cervical tumours >10 cm(3). Neoadjuvant chemotherapy in 22 patients (methotrexate 300 mg x m(-2) (with folinic acid rescue), bleomycin 30 mg x m(-2), cisplatin 60 mg m(-2)) was repeated twice weekly for three courses and followed by radical hysterectomy. Post-operative radiotherapy was given in 14 cases. A total of 23 patients treated either with radical surgery or chemoradiotherapy over the same time period comprised the nonrandomised control group. MR scans before and after neoadjuvant chemotherapy and in the control group documented tumour volume on imaging and metabolites on in vivo spectroscopy. Changes were compared using a paired t-test. Survival was calculated using the Kaplan-Meier method. There were no significant differences between the neoadjuvant chemotherapy and control groups in age (mean, s.d. 43.3+/-10, 44.7+/-8.5 years, respectively, P=0.63) or tumour volume (medians, quartiles 35.8, 17.8, 57.7 cm(3) vs 23.0, 15.0, 37.0 cm(3), respectively, P=0.068). The reduction in tumour volume post-chemotherapy (median, quartiles 7.5, 3.0, 19.0 cm(3)) was significant (P=0.002). The reduction in -CH(2) triglyceride approached significance (P=0.05), but other metabolites were unchanged. The 3-year survival in the chemotherapy group (49.1%) was not significantly different from the control group (46%, P=0.94). There is a significant reduction in tumour volume and -CH(2) triglyceride levels after neoadjuvant chemotherapy, but there is no survival advantage.

Figure 1

Tumour volumes pre and post neoadjuvant chemotherapy, showing response in individual cases.

Figure 2

Sagittal T2-weighted fast spin-echo (FSE 3000/88 ms (TR/effective TE)) images before (A) and after (B) three cycles of neoadjuvant chemotherapy. The intermediate signal intensity tumour confined to the cervix (arrows) reduced from 50 to 18 cm³ in volume.

Figure 3

Tumour volume distribution prior to treatment in the neoadjuvant chemotherapy group and the control group.

Figure 4

Proton magnetic resonance spectra (¹H PRESS, TR=1600 ms; TE=135 ms) acquired from a 3.75 cm³ voxel within the tumour before (A) and after (B) three cycles of neoadjuvant chemotherapy. Triglyceride signal (1.3 p.p.m.) in-phase with choline-containing compounds (3.2 p.p.m.) is reduced in (B).

Figure 5

Cumulative proportions surviving in each group. The solid line shows the Kaplan–Meier survival curve for the neoadjuvant chemotherapy group and the dashed line is the survival curve for the control group. The vertical dashes are censored observations and the open symbols are deaths.