Abstract
Scarce data exist on concurrent chemotherapy in locally advanced cervical cancer (LACC) patients (pts) treated with image-guided adaptive brachytherapy (IGABT). We examined the effect of a number of chemotherapy cycles and their interaction with brachytherapy dose/volume parameters. Clinical records of 209 consecutive pts treated for a LACC were reviewed. Pts received CRT concurrently with cisplatin 40 mg/m² or carboplatin AUC2. An additional cycle could have been delivered during the pulse-dose rate (PDR)-IGABT. The impact of a number of chemotherapy cycles on outcome was examined, as well as the interactions with dose volume parameters. The number of cycles was four in 55 (26.3%) pts, five in 154 (73.7%) including 101 receiving the fifth cycle during IGABT. Median follow-up was 5.5 years. Pts receiving five cycles had a better outcome on all survival endpoints, including three year local control rate (93.9% vs. 77.2%; p < 0.05). In the subgroup, only pts with tumor FIGO (Fédération Internationale de Gynécologie Obstétrique) stage ≤IIB or with CTVHR > 25 cm3 had a better outcome. Pts receiving four cycles with D90CTVHR > 80GyEQD2 had the same locoregional control–(LRC) as those receiving five cycles and achieving D90CTVHR ≤ 80 GyEQD2 (p = 0.75). An optimal propensity score matching the balance for the FIGO stage, CTVHR volume and D90CTVHR confirmed the effect, with the largest life expectancy benefit for locoregional failure-free survival (absolute gain: 1.5 years; p = 0.017). Long-term radiation-induced toxicity was not increased. Increasing the total number of cycles from 4 to 5 improved LFS, suggesting a place for systemic strategies aimed at in-field cooperation. Delivering an additional cycle at the time of brachytherapy did not increase morbidity and there permitted an increase in chemotherapy dose intensity.
Highlights
The benefit of concurrent chemoradiation (CCRT) in locally advanced cervical cancer (LACC) has been demonstrated for a long time, with large meta-analyses showing that the addition of chemotherapy to standard radiotherapy improved overall survival (OS) and progression-free survival (PFS), with absolute benefits of 10% and 13%, respectively
In a large institutional series of patients homogeneously treated with CCRT followed by image-guided adaptive brachytherapy (IGABT), we examined the effect of delivering an additional chemotherapy cycle concurrently with external irradiation and brachytherapy, and the extent of this effect according to brachytherapy dose/volume parameters
A previous study has examined prognostic factors for local control in 225 patients treated for LACC with IGABT, including 95% treated with CCRT
Summary
The benefit of concurrent chemoradiation (CCRT) in locally advanced cervical cancer (LACC) has been demonstrated for a long time, with large meta-analyses showing that the addition of chemotherapy to standard radiotherapy improved overall survival (OS) and progression-free survival (PFS), with absolute benefits of 10% and 13%, respectively. The place of chemotherapy has been poorly documented in the era of IGABT, as meta-analyses on the benefit of chemotherapy were conducted without image guidance and without dose escalation. The important role of chemotherapy in the systemic control in high-risk patients treated with IGABT has been shown, the effect of chemotherapy on local control and interaction with dose/volume parameters in the era of modern irradiation techniques remains unknown [14]. In a large institutional series of patients homogeneously treated with CCRT followed by IGABT, we examined the effect of delivering an additional chemotherapy cycle concurrently with external irradiation and brachytherapy, and the extent of this effect according to brachytherapy dose/volume parameters
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