Recommendations from Gynaecological (GYN) GEC-ESTRO Working Group☆ (I): concepts and terms in 3D image based 3D treatment planning in cervix cancer brachytherapy with emphasis on MRI assessment of GTV and CTV

doi:10.1016/j.radonc.2004.12.015

Radiotherapy and Oncology

Volume 74, Issue 3, March 2005, Pages 235-245

https://doi.org/10.1016/j.radonc.2004.12.015 Get rights and content

Summary

Background and purpose

Brachytherapy (BT) plays a crucial role in the management of invasive cervix cancer from stage I to IV. Intracavitary techniques are based on afterloading devices, with different types of applicators. CT and/or MRI compatible applicators allow a sectional image based approach with a better assessment of gross tumour volume (GTV) and definition and delineation of target volume (CTV) compared to traditional approaches. Accurate and reproducible delineation of GTV, CTV and PTV, as well as of critical organs has a direct impact on BT treatment planning, especially if it is possible to adapt the pear-shape isodose by optimisation using DVH analysis. When introducing a 3D image based approach for GTV and CTV assessment, there is a need for a common language to describe the concepts and to define the terms which are to be used.

Methods

In 2000, GEC-ESTRO decided to support 3D imaging based 3D treatment planning approach in cervix cancer BT with the creation of a Working Group. The task was to describe basic concepts and terms and to work out a terminology enabling various groups working in this advanced field to use a common language. The recommendations described in this report were proposed based on clinical experience and dosimetric concepts of different institutions (IGR, Leuven, Vienna) and were stepwise validated against the background of different clinical experience.

Conclusions

As GTV and CTV for BT change significantly during treatment, time frame for assessment of GTV and CTV for BT is specified in this report: at time of diagnosis GTV_D, CTV_D and at time of BT GTV_B, CTV_B. Furthermore, CTV for BT is defined related to risk for recurrence: high risk CTV and intermediate risk CTV. Beside verbal descriptions detailed examples are given, partly in form of schematic drawings.

Introduction

Brachytherapy (BT) plays a major role in the therapeutic management of patients with cervix cancer from stage I to IV. The rapid dose fall-off allows a very high dose to the central pelvis, while relatively sparing bladder, rectum, sigmoid and small bowel. Concomitant chemoradiation followed by BT represents the standard of care in patients with tumours larger than 4 cm, i.e. from stage IB2 to stage IVA. For stage IB1, BT is a treatment option as part of radical radiotherapy combined with external beam RT, or as a preoperative BT in combination with colpohysterectomy and lymphadenectomy [12]. If radiotherapy is considered, BT is generally a major part of treatment, delivering substantial dose to the tumour in the central pelvis while sparing the surrounding organs at risk [9].

Tumour volume (GTV) is well recognised as one of most important prognostic factors in terms of local control. Therefore, a complete coverage of GTV and the GTV related clinical target volume (CTV) is crucial and is to be expected to be related to a better outcome.

The implementation of treatment planning systems allows an individual adaptation of dose distribution to CTV in high dose-rate or pulsed dose-rate BT but also—however in a less extended procedure—in low dose-rate BT [3], [6], [9], [22], [31].

Target volume assessment is—even nowadays—first based on clinical examination with appropriate documentation in three dimensions [9]. If anterio-posterior and lateral dimensions are well accessible for clinical evaluation, the height of tumour may be clinically unaccessible, especially when the tumour extends to the endocervix and/or the endometrium. Nowadays, sectional imaging gives more valid and reliable information on individual tumour extension and configuration and its topography [2], [4], [7], [10], [13], [20], [23], [29], [35], [36]. By magnetic resonance imaging (MRI) tumour size and configuration have been proven to be more appropriately assessed compared to clinical examination or CT-scan [17], [21], [32], [34].

Accurate delineation of gross tumour volume (GTV), definition and delineation of CTV and PTV, as well as of critical organs has a direct impact on BT procedure, especially if it is possible to adapt the pear-shape isodose by optimisation allowing DVH analysis for a fixed dose and/or a fixed volume. It is clear that to apply these terms to utero-vaginal BT, a common language is needed [8], [14], [24].

Section snippets

Task of GYN GEC-ESTRO group

GEC-ESTRO decided in 2000 to support and promote 3D imaging based 3D treatment planning approach in cervix cancer BT. A Working Group (WG) was founded (Gynaecological (GYN) GEC-ESTRO WG), which was based on contribution of physicians and physicists from different centres actively involved in this field at that time. The task was to describe basic concepts and terms for this approach and to work out a terminology which would enable various groups working in this field to use a common language

3D image based approach: change of GTV during treatment

The development of 3D imaging based 3D treatment planning includes a new comprehensive approach for cervix cancer BT [6], [10].

The procedure is straightforward if BT is the sole method of treatment as in early disease or in a preoperative approach in limited disease. However, most patients are nowadays treated definitely with a combination of external beam therapy with simultaneous chemotherapy and BT. As GTV and topography change significantly during external beam therapy (with or without

Clinical approaches in treatment planning and performance

In promoting research and development of 3D image based BT, historical difficulties in communicating results in cervix cancer BT (‘mgh’-, ‘point A’-, ‘reference volume’-traditions, see in detail [6], [9]) should be overcome by using one terminology based on well understood concepts and terms from the beginning.

From the start of GYN GEC-ESTRO WG, it became clear that major different traditions existed also within this group, which would have a major impact on developing a 3D imaging based

GTV and CTV at diagnosis and at time of brachytherapy

Major difficulties had to be overcome to understand and combine the following ‘two worlds’:

*
‘CTV according to GTV at time of BT’ (coming from point A dose specification, with 80–90 Gy to this CTV)
*
‘CTV according to GTV at diagnosis’ (with 60 Gy to this CTV).

There was no way to understand and overcome these difficulties in concept and terminology just by theoretical discussion. Therefore, we decided to study treatment concepts and terminology by constructing a questionnaire and applying the

Protocol development 2001–2002: first steps

The first questionnaire (2001) was designed to prospectively collect information on following (Meeting Vienna 2/2001):

•
Dimensions and volumes of GTV, CTV as defined by clinical examination and by MRI:
- –
  at time of diagnosis
- –
  at time of BT (after external irradiation);
•
Dimensions and volumes of reference volume (60, 75, 90, and 120 Gy);
•
Volume of isodose going through point A;
•
Treated volume (prescribed dose);
•
Coverage in percent related to CTV and GTV;
•
DVH analysis for fixed doses and certain coverage

GTV and CTV delineation workshop I: Vienna 7/2003

As experience so far was mainly on certain shortcomings in defining a protocol for CTV and CTV related parameter assessment, it was decided to have an expert meeting (delineation workshop with theoretical and practical aspects) with a joint exercise in delineation process based on comparable clinical cases. Based on this experience, a further specification of the protocol was to be performed and be tested again in a joint evaluation.

A detailed clinical description based on an advanced 3D

Definition and delineation of GTV and CTV: final concept

The following recommendations were proposed based on clinical experience and dosimetric concepts of different institutions (IGR, Leuven, Vienna) and based on validation methodology as described in detail above. These target definitions take into account differences in BT target definition approaches with clinical traditions based on assessment of disease at diagnosis and others more based on extent of disease as it presents at time of BT.

*
The approach derived from using point A as a reference

Terms and concepts definition (GYN GEC-ESTRO protocol version 09/2004)

The target concept as proposed here is based in principle on three CTVs according to tumour load and hence to the risk for recurrence: a high risk CTV with a macroscopic tumour load and an intermediate risk CTV representing significant microscopic disease. In addition, a low risk CTV including potential microscopic tumour spread can be distinguished. The low risk CTV is treated by surgery and/or by external beam radiotherapy and is not dealt with in detail (Fig. 3).

Tumour load (GTV), true

Future considerations

MRI has been clearly demonstrated to be superior to any other imaging procedure in cervix cancer allowing an accurate definition of the tumour. This superiority has also been reported in literature when comparing MRI based treatment planning to radiography based conventional treatment planning approaches [15], [35].

The recommendations on definition and delineation of GTV and CTV are based on clinical experience and different dosimetric concepts. Development of 3D image based 3D treatment

References (36)

E. Briot et al.
Dose–volume histogram analysis for tumour and critical organs in intracavitary brachytherapy of cervical cancer with the use of MRI. Annual Brachytherapy Meeting GEC/ESTRO
Radiother Oncol
(2001)
E. Burghardt et al.
Magnetic resonance imaging in cervical cancer: a basis for objective classification
Gynecol Oncol
(1989)
R. Cetingoz et al.
Optimisation in high dose-rate brachytherapy for utero-vaginal applications
Radiother Oncol
(2001)
B. Erickson
The sculpted pear: an unfinished brachytherapy tale
Brachytherapy
(2003)
C. Fellner et al.
Comparison of radiography- and computed tomography-based treatment planning in cervix cancer in brachytherapy with specific attention to some quality assurance aspects
Radiother Oncol
(2001)
T.P. Hellebust et al.
Inter fraction variations in rectum and bladder volumes and dose distributions during high dose-rate brachytherapy treatment of the uterine cervix investigated by repetitive CT-examinations
Radiother Oncol
(2001)
N.A. Mayr et al.
Method and timing of tumour volume measurement for outcome prediction in cervical cancer using magnetic resonance imaging
Int J Radiat Oncol Biol Phys
(2002)
N.A. Mayr et al.
Tumour size evaluated by pelvic examination compared with 3-D MR quantitative analysis in the prediction of outcome for cervical cancer
Int J Radiat Oncol Biol Phys
(1997)
J. Nevinson et al.
CT based brachytherapy planning and complimentary bioeffect dosimetry: evaluation of combined brachytherapy and external beam radiotherapy dose distributions, in the treatment of cervical cancer
Radiother Oncol
(2001)
R. Pötter et al.
Definitive radiotherapy based on HDR brachytherapy with iridium 192 in uterine cervix carcinoma: report on the Vienna University Hospital findings (1993–1997) compared to the preceding period in the context of ICRU 38 recommendations
Cancer Radiother
(2000)

R. Pötter et al.

Survey of the use of ICRU 38 in recording and reporting cervical cancer brachytherapy

Radiother Oncol

(2001)

L.L. Subak et al.

Cervical carcinoma: computed tomography and magnetic resonance imaging for preoperative staging (Review)

Obstet Gynecol

(1995)

N. Wachter-Gerstner et al.

The impact of sectional imaging on dose escalation in endocavitary HDR-brachytherapy of cervical cancer: results of prospective comparative trial

Radiother Oncol

(2003)

N. Wachter-Gerstner et al.

Bladder and rectum dose defined from MRI based treatment planning for cervix cancer brachytherapy: comparison of dose-volume histograms for organ contours and organ wall, comparison with ICRU rectum and bladder reference point

Radiother Oncol

(2003)

J. Dimopoulos et al.

Systematic evaluation of MRI and clinical findings in cervical cancer at diagnosis and at time of brachytherapy: potential of MRI on delineation of GTV, patho-anatomical structures and organs at risk

Radiother Oncol

(2004)

J. Dimopoulos et al.

Combined MRI-based intracavitary and interstitial brachytherapy for locally advanced cervical cancer with a modified tandem ring applicator-clinical feasibility and preliminary results

Radiother Oncol

(2004)

S. Fromm et al.

Correlation between the treated volume, the GTV and the CTV at the time of brachytherapy and the histopathologic findings in 33 patients with operable cervix carcinoma

Radiother Oncol

(2002)

A. Gerbaulet et al.

Cervix cancer

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HF_pre was the strongest predictor of DFS, but a significant correlation with outcome was found also for volume regression. The combination of HF_pre and volume regression showed a stronger association with DFS than HF_pre alone. Patients with disease recurrence were selected to either the intermediate- or high-risk group with a 100 % accuracy. Functional regression showed a stronger correlation to HF_pre than volume regression.
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End-to-end dosimetry audit for brachytherapy is challenging due to the steep dose gradient. However, it is an efficient method to detect unintended errors in actual clinical practice.
We aimed to develop an on-site end-to-end test phantom for three-dimensional image-guided brachytherapy (IGBT) for cervical cancer.
The test phantom we developed consisted of a water tank with an applicator/detector holder. The holder was designed to accommodate the applicator and insert an ionization chamber (PinPoint; PTW, Freiburg, Germany) to measure the dose at point A. Imaging and reconstruction were performed in the same way as performed for a patient. The feasibility of our test phantom was assessed in two different hospitals using tandem and ovoid (made of either metal or carbon) applicators that the hospitals provided.
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Definitive radiation for advanced cervix cancer is not associated with vaginal shortening—a prospective vaginal length and dose correlation
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Prospectively measure change in vaginal length after definitive chemoradiation (C-EBRT) with Intracavitary Brachytherapy (ICBT) for locally advanced cervix cancer (LACC) and correlate with vaginal dose (VD).
Twenty one female patients with LACC receiving C-EBRT and ICBT underwent serial vaginal length (VL) measurements. An initial measurement was made at the time of the first ICBT procedure and subsequently at 3 month intervals up to 1 year post radiation. The vagina was contoured as a 3-dimensional structure for each brachytherapy plan. The difference in VL before and at least 6 months after the last fraction of brachytherapy was considered as an indicator of toxicity.
The mean initial VL was 8.7 cm (6.5–12) with median value of 8.5 cm. The mean VL after 6 months was 8.6 cm (6.5–12) and VL change was not found to be statistically significant. The median values (interquartile ranges) for vaginal D0.1cc, D1cc, and D2cc were 129.2 Gy (99.6–252.2), 96.9 Gy (84.2–114.9), and 89.6 Gy (82.4–102.2), respectively. No significant correlation was found between vaginal length change and the dosimetric parameters calculated for all patients.
Definitive C-EBRT and ICBT did not significantly impact VL in this prospective cohort probably related to acceptable doses per ICRU constraints. Estimate of vaginal stenosis and sexual function was not performed in this cohort which is a limitation of this study and which we hope to study prospectively going forward.
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Historical gynecologic interstitial brachytherapy templates block direct tumor visualization during needle placement, presenting an opportunity for clinical innovation to develop a novel interstitial template allowing direct tumor visualization during needle insertion.
We designed and implemented a novel interstitial template, simple needle attachment post placement interstitial template (SNAPP-IT), that allowed direct visualization of the target vaginal tumor during interstitial needle placement while maintaining the ability to individually secure needles to the template, allow a vaginal cylinder, suture holes for securing to the perineum, MRI compatibility and sterilizable for repeat use. Procedure outcomes including procedure time, needle path lengths, and plan dosimetry were prospectively captured in a patient database.
Forty gynecologic interstitial brachytherapy cases were recorded (20 SNAPP-IT, 20 traditional templates). Needle insertion depth was reduced using the SNAPP-IT in comparison with traditional interstitial templates (11.8 cm vs. 3.6 cm, p < 0.0001). The average CTV volume was 25.6 cc for SNAPP-IT and 20.7 cc for traditional; both methods averaged a similar number of needles (15.8, 15.6). Dosimetric constraints were similarly met in both treatment groups. Procedures performed using the SNAPP-IT were shorter compared with those performed with traditional interstitial devices (83.4 minutes vs. 100.7 minutes) and there were no post-operative infections in the SNAPP-IT group.
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To evaluate the possibility of dose escalation and reduction of fraction number in cervical brachytherapy using a gel spacer.
Twenty patients with uterine cervical cancer treated with image-guided adaptive brachytherapy (IGABT) were selected. Hyaluronic acid gel injection (HGI) was performed in the rectovaginal and vesicouterine septum for 10 patients. The other ten patients were not with HGI. Both groups were treated with IGABT involving tandem/ovoid or cylindrical applicators along with additional interstitial needles. Dose distributions approved by radiation oncologists were retrospectively analyzed, and a dose summation of 45 Gy/25 of external beam radiation therapy and IGABT was performed. Dose constraints for D_2cc of bladder, rectum, and sigmoid were 80, 70, and 70 Gy, respectively. Equivalent dose in 2-Gy fractions calculations used α/β = 10 Gy for high-risk clinical target volume (CTV_HR) D₉₀ and α/β = 3 Gy for organs at risks (OARs). As a planning study, dose distribution rescaling was conducted to deliver as much dose to CTV_HR D₉₀ as possible within the dose constraint limitation for OARs when IGABT was performed for four, three, and two fractions in both groups.
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: GYN GEC-ESTRO Working Group has been supported by an unrestricted grant from VARIAN to ESTRO.

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Recommendations from Gynaecological (GYN) GEC-ESTRO Working Group☆ (I): concepts and terms in 3D image based 3D treatment planning in cervix cancer brachytherapy with emphasis on MRI assessment of GTV and CTV

Summary

Background and purpose

Methods

Conclusions

Introduction

Section snippets

Task of GYN GEC-ESTRO group

3D image based approach: change of GTV during treatment

Clinical approaches in treatment planning and performance

GTV and CTV at diagnosis and at time of brachytherapy

Protocol development 2001–2002: first steps

GTV and CTV delineation workshop I: Vienna 7/2003

Definition and delineation of GTV and CTV: final concept

Terms and concepts definition (GYN GEC-ESTRO protocol version 09/2004)

Future considerations

Radiother Oncol

Gynecol Oncol

Radiother Oncol

Brachytherapy

Radiother Oncol

Radiother Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Radiother Oncol

Cancer Radiother

Radiother Oncol

Obstet Gynecol

Radiother Oncol

Radiother Oncol

Systematic evaluation of MRI and clinical findings in cervical cancer at diagnosis and at time of brachytherapy: potential of MRI on delineation of GTV, patho-anatomical structures and organs at risk

Radiother Oncol

Combined MRI-based intracavitary and interstitial brachytherapy for locally advanced cervical cancer with a modified tandem ring applicator-clinical feasibility and preliminary results

Radiother Oncol

Correlation between the treated volume, the GTV and the CTV at the time of brachytherapy and the histopathologic findings in 33 patients with operable cervix carcinoma

Radiother Oncol

Cervix cancer

Recommendations from Gynaecological (GYN) GEC-ESTRO Working Group^☆ (I): concepts and terms in 3D image based 3D treatment planning in cervix cancer brachytherapy with emphasis on MRI assessment of GTV and CTV