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

TABLE 3 RISK-ADAPTED BRACHYTHERAPY DOSE PRESCRIPTION PROTOCOL FOR EMBRACE-II Target D 90 CTV HR EQD2 10 D 98 CTV HR EQD2 10 D 98 GTV res EQD2 10

D 98 CTVI R EQD2 10

Point A

>90 Gy <95 Gy

Planning aims

>75 Gy

> 95 Gy

> 60 Gy

>65 Gy

Limits for prescribed dose

>85 Gy

> 90 Gy

-

ICRU recto- vaginal point EQD2 3

Bladder D2cm 3 EQD2 3

Rectum D2cm 3 EQD2 3

Sigmoid D2cm 3 EQD2 3

Bowel D2cm 3 EQD2 3

OAR

Planning aims

<80 Gy

<65 Gy

<65 Gy

<70 Gy

<70 Gy

Limits for prescribed dose

<90 Gy

<75 Gy

<75 Gy

<75 Gy

<75 Gy

Preclinical and clinical studies have shown that prolongation of overall treatment time (OTT) is detrimental to patient outcome due to repopulation of tumour clonogens [12]. Analysis of data from the Retro-EMBRACE study [27] suggested that an increase in OTT of 1 week is equivalent to a reduction of CTV-T_HR dose by 5 Gy. In the EMBRACE-II study, it is recommended that the OTT from the first EBRT fraction to the final BT fraction should be ≤50 days. 9.2 Dose constraints The EQD2 concept has allowed the BT equi-effective dose to be combined with the equi-effective dose of different EBRT schedules into a single value which can then be used as a dose constraint for BT dose optimisation. Clinical data based on schedules with a homogenous dose of 45-50Gy whole pelvis EBRT and 40-45Gy of HDR or PDR BT have allowed robust dose constraints for the various target volumes and OAR to be identified [28] and planning aims (as defined in chapter 8.6 of ICRU Report 89) have been introduced. As the target and OAR constraints are often conflicting, hard and soft constraints have been defined for each target volume and OAR to allow for compromises as shown in Table 3. The ability to achieve certain dose constraints depends much on the availability of IC/IS applicators, as IC applicators have significant limitations in large or asymmetrical tumours to reach a high target dose with good OAR sparing. Also, with MRI-based IGABT, target contouring and dose evaluation are more precise and different prescription protocols with different dose planning aims can therefore be applied for different clinical environments e.g. with or without MRI with applicator in place or with or without access to IC/IS applicators. The relative dose contribution from EBRT and BT is also important when selecting EQD2 constraints for certain volumes of OAR, as changing the dose contribution of EBRT compared with BT will significantly influence the dose–effect curves for an OAR. 9.3 Implant geometry The choice of implant geometry is based on tumour, target and OAR topography at the time of BT, individual patient anatomy and institutional practice. The intravaginal component, such as ovoids

Figure 14. Typical median volumes and mean doses for cervical IGABT Unpublished data from EMBRACE I (n=1300) and EMBRACE II (CTV-T LR init , n=168). Initial median GTV-T in EMBRACE II is 55 cm 3 . The anatomical location of the GTV-T init at the time of diagnosis is reflected in the CTV-T_IR defined at BT; this region received a median near minimum dose of 62 Gy in EMBRACE I. In good-responding tumours, the dose at the limits of the GTV-T init is 60-70 Gy, while in poor-responding tumours the region of GTV init may receive doses similar to the CTV-T HR (e.g., around 80 Gy) (Reprinted from Semin. Radiat. Oncol., 29/3, Tan LT, Tanderup K, Kirisits C, et al , Image-guided Adaptive Radiotherapy in Cervical Cancer, 284-298, 2019, with permission from Elsevier).

The whole pelvis is usually treated with EBRT to 45–50 Gy at 1.8-2 Gy/fraction followed by BT to reach total EQD2 values of 85 to 95 Gy for the D90% of the CTV-T_HR (Figure 14) [19]. It is important to avoid a heterogeneous EBRT dose in the central part of the pelvis, e.g., from the use of midline blocks, as this may invalidate the calculation of the combined dose from EBRT and BT particularly to adjacent OAR. The optimal timing of BT in relation to EBRT can be adapted depending on the initial size of the tumour, the response to EBRT and the BT fractionation schedule. For advanced disease and large tumours, significant tumour regression (70-80%) often occurs during the first 3-4 weeks of EBRT and the use of BT after or towards the end of EBRT can greatly improve target coverage and facilitate a response-adapted BT prescription resulting in an improved therapeutic ratio.