Simultaneous Integrated Parametrial/Sidewall Boosts for Cervical Cancer: Late Toxicity and Outcomes.

Abstract

The purpose of this study was to evaluate the safety of intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) to the parametrium/paracervical tissue among women with locally advanced cervical cancer. In this IRB approved retrospective study, women with intact cervical cancer treated in a single institution with definitive radiation therapy followed by brachytherapy (BT) boost from 2011 through 2016 were identified. Women treated with SIB technique to either one or both parametria were included. Acute and late toxicities (defined by the CTCAE v 4.0), recurrences (local, sidewall, and distant), and overall survival were analyzed via the Kaplan Meier method. Forty-three women with bulky stage IB1-IVB cervical cancer were treated with curative intent radiotherapy from May 2011 to June 2016 (IB1 n=2, IB2 n=7, IIB n=22, IIIA n=2, IIIB n=9, IVB n=1). All women received external beam radiotherapy (EBRT) to the whole pelvis (45-51.4 Gy/ 24-25 fractions) as well as a unilateral or bilateral parametrial boosts (53.6-60 Gy/ 24-25 fractions) given with SIB technique. Nodal disease received additional dose in 35 women (55-70 Gy/ 24-36 fractions). All women except for one received concurrent cisplatin. At the conclusion of EBRT, brachytherapy was delivered to a total goal EQD2 dose of 75-87Gy. Median follow-up time was 25.2 months. Rates of acute grade ≥2 gastrointestinal (GI), genitourinary (GU), and hematologic (heme) toxicities were 39.5%, 7.0%, and 55.8% respectively; acute grade ≥3 toxicities were 7.0%, 2.3%, and 16.3% respectively. There were no acute grade 4 toxicities. Two-year rates of late grade ≥2 GI and GU toxicities were 33.5% and 10.4% respectively; two-year late grade ≥ 3 toxicities were 12.0% and 6.2% respectively. There were two grade 4 GI toxicities, both rectovaginal fistulas. Two-year overall survival and local control rates were 82.1% and 89.4% respectively. Univariate analysis showed a significant association between late grade ≥ 3 GI toxicity and BT rectal D2cc dose (p=0.041, HR=1.210, 95% CI 1.008-1.453). Patients with cumulative rectal D2cc EQD2 dose ≥75Gy had a significantly higher rate of late grade ≥ 3 GI and GU sequelae compared to those <75Gy (66.7% vs. 2.5% with p=0.001 and 66.7% vs. 0% with p=0.004, respectively). IMRT-SIB is a feasible technique allowing for dose escalation to the parametria and sidewall, with overall toxicity rates similar to conventional technique. Late GI toxicity appears to be highly dependent upon cumulative rectal dose; when the rectal D2cc was below 75Gy EQD2, toxicity rates were low. If SIB technique is considered in the low pelvis, it may be prudent to consider strict adherence to rectal dose constraints at brachytherapy.