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Report of the GEC ESTRO Gynaecology Working Group and Network

 

Overall aim of the Working Group

The Groupe Européen de Curiethérapie (GEC) ESTRO gynaecology (gyn) working group (WG) aims to facilitate networking across research and development, clinical studies and education in gynaecological brachytherapy (BT) and external beam radiotherapy (EBRT). The WG aims to initiate and contribute to international guidelines that involve gynaecological BT. It collaborates with other international societies to facilitate synergy and consensus and to ensure that guidelines and other projects have a broad impact.

 

Annual WG network meeting

The GEC ESTRO gyn WG organises an annual meeting that runs back-to-back with the GEC ESTRO workshop: ESTRO gyn network meeting. The purpose of the network meeting is to present and discuss activities taking place within the WG, share knowledge and preliminary data to help the development of future gynaecology research activities, and bring in experts from other societies to inspire the ESTRO gyn network and facilitate collaboration. The meeting broadly covers general topics relevant to gynaecological radiotherapy, such as clinical studies, EBRT and BT techniques, target/dose/fractionation, morbidity, combination therapy (chemotherapy, targeted / immunotherapy, hyperthermia), oligometastatic/recurrent disease, re-irradiation and radiobiology. A call for topics and presenters is initiated annually. During the COVID-19 pandemic, the meeting was developed into a hybrid version so that attendees had the opportunity to attend online. The meeting in 2021 was fully online; the 2022 gathering was hybrid, with the in-person version in Nice, and in 2023 the in-person section was held in Prague.

Coordinator: Kari Tanderup

 

Gyn-SMART webinars

The series on modern applied radiotherapy (SMART) has been introduced by the gyn network recently. It is a quarterly programme of one-hour webinars that are focused on practical aspects of gynaecological radiotherapy. The latest recommendations, panel discussions with experts and clinical cases are presented. The webinars are interdisciplinary and aim to cover aspects relevant to medical doctors, medical physicists and radiotherapy technologists. You can find more information at https://sites.google.com/view/gyn-smart.

Coordinators: Sofia Spampinato, Kari Tanderup, Monica Serban, Gemma Eminowicz, Simon Duke, Remi Nout

 

Recent and ongoing GEC ESTRO recommendations and guidelines

The GEC ESTRO gyn WG has a long track record of developing international recommendations. A main achievement is that GEC ESTRO recommendations have facilitated broad international dissemination of MRI-guided BT-gamma for use to treat cervical cancer during the last two decades, and these recommendations have been expanded recently to cover CT-guided cervix BT and treatment for vaginal cancer and vaginal recurrences. GEC ESTRO has also collaborated with other societies such as the European Society of Gynaecological Oncology (ESGO), the American Brachytherapy Society (ABS) and the Indian Brachytherapy Society (IBS).

Please find below an overview of recommendations and guidelines that have been published since 2021 and those that are in progress.

  • IBS-GEC ESTRO-ABS recommendations for CT-based contouring in image-guided adaptive brachytherapy for cervical cancer. (Mahantshetty U, Poetter R, Beriwal S, Grover S, Lavanya G, Rai B, Petric P, Tanderup K, Carvalho H, Hegazy N, Mohamed S, Ohno T, Amornwichet N. Radiother Oncol. 2021 Jul; 160:273-284).
  • GEC-ESTRO (ESTRO guidelines committee)-ABS-Canadian Brachytherapy Group consensus brachytherapy target definition guidelines for recurrent endometrial and cervical tumours in the vagina. (Kamrava M, Leung E, Bachand F, Beriwal S, Chargari C, D'Souza D, Erickson B, Fokdal L, Han K, Harkenrider M, Lin L, Mahantshetty U, Nesvacil N, Ravi A, Schmid M, Vigneault E, Westerveld H, Yashar C, Nout R. Int J Radiat Oncol Biol Phys. 2023 Mar 1;115(3):654-663).
  • ESGO/ESTRO/European Society of Pathology (ESP) guidelines for the management of patients with cervical cancer - update 2023. (Cibula D, Rosaria Raspollini M, Planchamp F, Centeno C, Chargari C, Felix A, Fischerová D, Jahnn-Kuch D, Joly F, Kohler C, Lax S, Lorusso D, Mahantshetty U, Mathevet P, Raj Naik M, Nout RA, Oaknin A, Peccatori F, Persson J, Querleu D, Rubio Bernabé S, Schmid MP, Stepanyan A, Svintsitskyi V, Tamussino K, Zapardiel I, Lindegaard J. Radiother Oncol. 2023 Jul; 184:109682).
  • ESGO/ESTRO quality indicators for radiation therapy of cervical cancer. (Chargari C, Tanderup K, Planchamp F, Chiva L, Humphrey P, Sturdza A, Tan LT, van der Steen-Banasik E, Zapardiel I, Nout RA, Fotopoulou C. Radiother Oncol. 2023 Jun; 183:109589).
  • ESTRO/ESGO/European Society for Paediatric Oncology (SIOPE) guidelines for the management of patients with vaginal cancer. (Nout RA, Calaminus G, Planchamp F, Chargari C, Lax S, Martelli H, McCluggage WG, Morice P, Pakiz M, Schmid MP, Stunt J, Timmermann B, Vokuhl C, Orbach D, Fotopoulou C. Int J Gynecol Cancer. 2023 Aug 7;33(8):1185-1202. Radiother Oncol. 2023 Sep; 186:109662).
  • GEC ESTRO-IBS-ABS recommendations for treatment planning in cervix brachytherapy (lead: Tanderup): in progress.
  • Project in preparation: contemporary approach to treatment planning and dose reporting for image-guided adaptive BT (IGABT) of vaginal cancer.

 

Recent and upcoming clinical studies

The WG supports clinical studies that are designed to provide clinical evidence for new treatment approaches through the use of advanced radiotherapy technology. These multi-centre studies have facilitated a large research portfolio, and the results have supported the continuous development of new clinical treatment approaches and recommendations.

 

EMBRACE II

EMBRACE II is aimed to implement interventions in terms of the systematic use of intracavitary/interstitial application techniques; dose prescription protocols for IGABT; tumour-related target concepts for EBRT (at diagnosis) and the selection of risk adaptive elective nodal targets for intensity-modulated radiotherapy (IMRT); and the risk-adaptive margin concept for use in image-guided radiotherapy (IGRT) (with a ratio of internal target volume to planning target volume of 5mm). The idea is to benchmark an outstanding level of local, nodal, systemic control and overall survival, and excellent morbidity and quality-of-life (QoL) outcomes, all of which are related to well-defined intervention strategies for IGABT, IMRT/IGRT and radio-chemotherapy. There is ongoing research into the links between EBRT and BT characteristics and acute morbidity.

Coordinators: Richard Pötter, Kari Tanderup, Ina Jürgenliemk Schulz, Christian Kirisits, Remi Nout, Max Schmid

Patient enrolment: from 2016-2021; 1452 patients

 

Translational research: EMBRACE I and II

IQ EMBRACE involves the collection of functional MR images from around 100 patients who were treated in EMBRACE II. IQ EMBRACE aims to link imaging data to clinical outcomes (work in progress).

Coordinators: Petra van Houdt, Uulke van der Heide, Kari Tanderup

BIO EMBRACE: Tissue taken from EMBRACE-I patients has been paraffin-embedded, collected from multiple international sites and immunohistochemically stained. Molecular biomarkers are being evaluated to link patterns of biomarker expression to retrospective and prospective clinical outcomes. At the time of writing, the final analysis was due to be presented at the International Gynaecological Cancer Society’s congress, IGCS 2023 (November 5-7 in Seoul, Korea), as part of the focused plenary session. The manuscript is at an advanced stage of preparation.

Coordinators: Supriya Chopra, Remi Nout

 

EMBRAVE

A prospective, multi-centre, clinical registration study on the use of radiochemotherapy and IGABT to treat vaginal cancer (EMBRAVE) has been launched and the first patients have been enrolled. This study will follow the EMBRACE-I template with the aim of evaluating the target concept, which is to benchmark results and derive evidence-based recommendations regarding dose planning and dose constraints for vaginal cancer. It is planned that this study will be amended to include vaginal recurrence tumours.

Principal investigator: Remi Nout

Patient enrolment: ongoing (began in 2023) for primary vaginal cancer

 

RetroCOSMOS

The RetroCOSMOS study is designed to build evidence on the role of radiotherapy and re-irradiation in the context of (oligo)metastatic and recurrent cervical cancer. This international, multicentre, retrospective cohort study opened in September for inclusion of patients via an electronic web-based case report form system. So far, 25 patients have been registered. The participating centres will discuss the potential for re-irradiation on a case-by-case basis every three months. The first such meeting was on 5 October and involved 40 participants. These discussions will be open to study participating sites and interested members.

Coordinators: Supriya Chopra, Remi Nout

Patient registration: ongoing (initiated 2023)

 

EMBRACE high-risk study

In this extension to the EMBRACE study, the addition of immunotherapy and anti-vascular endothelial growth factor will be tested in high-risk patients and those who have responded poorly to EBRT. The immunotherapy will be positioned close to the BT source in an attempt to synergise immunotherapy and high-dose radiotherapy. The study is expected to begin recruitment in mid-2024.

Coordinators: Remi Nout, Supriya Chopra, Ingrid Boere

 

EMBRACE de-escalation

The EMBRACE de-escalation study is aimed at reducing levels of treatment-related acute and late morbidity in low-risk cervical cancer patients through de-escalation of doses and volumes that are used in EBRT and through the use of combined EBRT+BT doses. The overall treatment time and numbers of EBRT and BT fractions will be reduced to lessen the burden of the treatment for the patients and improve efficiency for the hospitals. It is hypothesised that for some patients, radiotherapy can be de-escalated without any compromise of pelvic control. Since the optimal radiotherapy dose for low-risk patients is unknown, the aim is to investigate dose de-escalation in a stepwise manner. If interim results are favourable, de-escalation can be increased early in the study with continuous monitoring of safety through tests of pelvic control.

Coordinators: Remi Nout, Kari Tanderup

Patient enrolment: planned from the beginning of 2024

 

CT EMBRACE registration study

This study is designed to introduce the use of CT-based 3D-4D BT to treat patients with locally advanced cervical cancer. It will be a multicentre project within the framework of a prospective observational study, and thereby the aim is to establish a benchmark for clinical outcomes after the use of CT-based BT in a large patient population with respect to local control, survival, morbidity and QoL. Furthermore, another aim is to establish a reference for image-based dose-volume histogram (DVH) parameters according to the guidelines from the GEC ESTRO WG for CT IGABT settings, and to correlate image-based DVH parameters for clinical target volumes and organs at risk with outcomes.

Coordinator: Umesh Mahantshetty

Status: protocol in preparation

 

MR EMBRACE registration study

The aim of this study is to collect real-world data regarding cervical cancer patients who have been treated through the use of either standard-of-care radiochemotherapy, which includes MRI-guided BT, according to the ESGO-ESTRO-ESP guideline; or alternative schedules for unsuitable or frail patients. The study will also facilitate the prescription of evidence-based doses by providing a decision-support tool.

Coordinator: Max Schmid

Status: protocol in preparation

 

Guidelines for definitive treatment of endometrial cancer

As part of a multicentre study regarding treatments for endometrial cancers, data have been collected retrospectively regarding the treatment of 183 patients with BT alone or with EBRT+BT. Two results papers have been published. References are listed below.

Coordinator: Ángeles Rovirosa

  • Exclusive 3D-brachytherapy as a good option for stage-I inoperable endometrial cancer: a retrospective analysis in the gynaecological cancer GEC-ESTRO Working Group. Rovirosa A, Zhang Y, Chargari C, Cooper R, Bownes P, Wojcieszek P, Stankiewicz M, Hoskin P, Van der Steen-Banasik E, Segedin B, Najjari D, Pötter R, Tanderup K, Van Limbergen E. Clin Transl Oncol. 2022 Feb;24(2):254-265.
  • Stages I–III inoperable endometrial carcinoma: a retrospective analysis by the gynaecological cancer GEC-ESTRO working group of patients treated with external beam irradiation and 3D-image-guided brachytherapy. Rovirosa A, Zhang Y, Tanderup K, Ascaso C, Chargari C, Van der Steen-Banasik E, Wojcieszek P, Stankiewicz M, Najjari-Jamal D, Hoskin P, Han K, Segedin B, Pötter R, van Limbergen E, Cancers 2023, 15(19), 4750.

 

Collaboration with IGCS on education for low- and middle-income countries

In 2023, the IGCS established a consortium comprising several specialist organisations (ABS, IGCS, ESTRO, the American Association of Physicists in Medicine and the American Society for Radiation Oncology) to formalise and strengthen radiotherapy education and training for radiation oncology specialists in gynaecology in low and middle-income countries (LMICs). The consortium is developing a one-year programme that is designed to support the development of gynaecology radiotherapy services in hospitals in LMICs through the provision of ongoing, hands-on support to enable effective and safe implementation of modern radiotherapy techniques. This programme will consist of a balance of guided web-based and in-person learning with case-based education (which will include the involvement of virtual tumour boards through the extension for community healthcare outcomes (ECHO) project), lectures, and training sessions.

Coordinator from IGCS: Alexandra Taylor. Contributors from ESTRO: Remi Nout, Kari Tanderup, Kjersti Bruheim, Taran Hellebust

 

Get in touch with the GEC ESTRO gyn WG

Please contact the WG chair, Kari Tanderup, to be signed up to receive communications related to GEC ESTRO gynaecology activities and announcements of meetings including the gyn-SMART webinars. Email: karitand@rm.dk.

 

Acknowledgements

Organisation of activities in the GEC ESTRO gyn WG and related studies (e.g. development, coordination and management), projects and education is the work of a large group of enthusiastic colleagues who contribute their time voluntarily. The WG is indebted to all these individuals and to patients who participate in clinical studies to help provide the evidence for our field to move forward.

 

Kari Tanderup

Aarhus University Hospital

Denmark