16. Cervix cancer - The GEC-ESTRO Handbook of Brachytherapy

Cervix cancer

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THE GEC ESTRO HANDBOOK OF BRACHYTHERAPY | Part II Clinical Practice Version 1 - 01/09/2023

when the total dose to point A exceeded 75 Gy (4% vs 9%). The dose to the latero-pelvic wall was a significant factor influencing small bowel complications: the complication rate was <1% with a total dose of ≤50 Gy, 2% with 50-60 Gy, and 5% with higher doses. Several clinical studies have shown a correlation between rectal complications and the absorbed dose at the ICRU rectal reference point [82-86].There is also correlation between the Point A dose and the dose at the rectal reference point [84]. In contrast, the ICRU bladder reference point, although simple to find and reproducible, was reported not to correlate well with bladder adverse effects in earlier studies [82, 87, 88] although it appears more promising in recent EMBRACE studies, in particular for urinary frequency and incontinence [89]. For IGABT, Tanderup et al. [28] reviewed the correlations between dose in volumes and at points and OAR morbidity for several endpoints as comprehensively analysed in the EMBRACE-I study. An analysis of 1153 patients without bladder infiltration in the first EMBRACE study showed that an increase from 75 Gy to 80 Gy in bladder D2 cm 3 resulted in an increase from 8% to 13% for 4-year actuarial estimate of G≥2 cystitis [90]. For late rectal morbidity, an analysis of 960 patients showed that a rectal D2 cm 3 ≥75Gy was associated with a 12.5% risk of fistula at 3 years vs 0-2.7% for lower doses. A rectal D2 cm 3 <65Gy was associated with a two times lower risk of proctitis than a D2 cm 3 ≥65Gy [74]. More recently, it was shown that bowel D2 cm 3 correlated with G≥3 sigmoid and colon/small bowel events, and moderate/persistent diarrhoea and flatulence [91, 92]. Point doses (ICRU recto-vaginal, bladder and PIBS reference points) have also been shown to predict rectal, urinary and vaginal complications [93]. Examples of dose effect curves for various vagina (stenosis) and bladder (bleeding, cystitis, frequency, incontinence) morbidity endpoints are shown in figures 27-29. Dose levels of < 50 Gy for PIBS EBRT+BT and < 5 Gy for PIBS-2 cm EBRT are associated with lower risk of vaginal stenosis (Figure 30 [93]). The correlation between irradiated volume and complications has also long been recognised. Barillot et al. [94] analysed 642 patients treated with radiotherapy alone between 1970 and

1994. The analysis was divided into 3 periods: 1970-1978 (use of standard prescriptions),1979-1984 (implementation of individual adjustments), 1985-1994 (systematic individual adjustments). The height weight thickness of the 60 Gy volume (combined intracavitary and external irradiation) reduced over time from 842 cm 3 vs. 503 cm 3 on average; this was associated in a decrease in rate of G3 complications from 16% to 6%. For IGABT, a comparable dose parameter to the 60 Gy volume is the isodose surface volume (ISV) which is calculated using a predictive model based on Total Reference Air Kerma and compared to Point A-standard loading systems [45]. The ISV is also applicable to combined IC/IS implants [41] and has the potential to become an important straightforward treatment parameter to investigate factors inducing morbidity. 13.2 Impact of BT technique Several groups have shown that the BT technique can influence risk of complications. Kuske et al. [95] from Washington University compared the incidence of complications in 293 patients treated either with mini vaginal colpostats or with the standard Fletcher-Suit applicator. In this series, G3-4 complications occurred in 15% of patients treated with the mini-colpostats compared to 8% in those treated with the standard applicator. The use of vaginal cylinders has been reported by Barillot et al. [94] as a powerful predictive factor for complications although this may reflect a selection of worse cases not suitable for a standard technique. In contrast, in the Clatterbridge series of 226 patients all routinely treated with a vaginal cylinder [96], the 5-year actuarial rate of G2-3 bowel or urinary toxicity was only 3.1%. In the Retro-EMBRACE study, the use of the combined IC/IS technique [71] did not result in increased OAR dose or complication rate. There was no significant difference in late actuarial G3–5 bladder or gastro-intestinal morbidity between the IC and IC/IS groups (gastrointestinal 3–5%, bladder 2–4%) [29, 62]. For vaginal morbidity, however, there was a trend of higher actuarial G2–5 as well as G3–5 morbidity in the IC/IS group (p = 0.08) [71]. In a cohort of patients with distal parametrial and pelvic wall disease treated with additional oblique needles [72], G3-4 late toxicities were observed in 14/69 (20%) patients.

14. KEY MESSAGES

• Brachytherapy is crucial for optimal local control and cure in definitive radiotherapy for cervical cancer. • Pelvic control rates of around 90% can be achieved across all stages with MRI-based Image Guided Adaptive Brachytherapy without increasing morbidity. • The mainstay of cervical cancer BT remains the intracavitary applicator comprising an intrauterine tandem and an intravaginal component (ring or ovoids). • The addition of interstitial needles to supplement the dose from the intracavitary applicator improves local control rates in patients with large residual tumours or unfavourable topography at the time of BT. • IGABT target and OAR contouring and dose prescription, recording and reporting should comply with ICRU89/GEC-ESTRO recommendations. • EBRT and BT doses delivered using different fractionation schedules at different dose rates should be converted into an equi effective dose using the EQD2 concept. • The combined EBRT and BT EQD2 for target and OAR should be used as dose constraints for BT dose optimisation and should be based on available clinical evidence.