This is a Multicentre International Study Evaluating CT-based IGABT With / Without Either TRUS During BT/Pre BT MR as Per IBS-GECESTRO-ABS Recommendations for Target contouring-as an Alternative to MRIGABT for Cervical Cancer From Implementation Perspectives Under EMBRACE-III:TRIPLET IMPACT Study.

NCT07249021 | Not Yet Recruiting DMC

• 1 other identifier: IEC/0725/12000090/001
• Study Type: observational
• Target: 1,200
• Locations: 1 country
• Sites: 1

Brief Summary

Title: Integration of Multi-modality Imaging Protocols with Emphasis on CT in Image-Guided Adaptive Brachytherapy (IGABT) for Cervical Cancer - EMBRACE III-TRIPLET : IMPACT Study Locally advanced cervical cancer (LACC) remains a major health challenge, particularly in low- and middle-income countries (LMICs), which account for the majority of global cases. The standard curative treatment involves a combination of external beam radiotherapy (EBRT) with concurrent chemotherapy, followed by brachytherapy (BT). Brachytherapy plays a crucial role in achieving high local control by delivering radiation directly to the tumour through internally placed radioactive sources. Historically, BT dose prescription was based on two-dimensional (2D) X-ray images and defined anatomical "points," achieving 5-year local control rates of 60-70%. Over the last decade, magnetic resonance imaging (MRI)-based image-guided adaptive brachytherapy (MR-IGABT) has transformed practice by enabling three-dimensional (3D) target-based dose prescription and adaptation to tumour regression. The landmark EMBRACE I study, involving over 1300 patients, demonstrated over 90% 5-year local control rates with MR-IGABT, establishing it as the international gold standard endorsed by NCG, ICRU, NCCN, and ESGO-ESTRO guidelines. However, MRI-based planning for IGABT remains logistically and financially challenging for many centres, especially in LMICs. CT and transrectal ultrasound (TRUS) have emerged as feasible alternatives, offering broader accessibility. Despite encouraging outcomes from smaller institutional studies, the lack of standardized and validated target delineation concepts for CT-IGABT has led to significant variability in clinical implementation. Recognizing this, the Indian Brachytherapy Society (IBS), American Brachytherapy Society (ABS), and GEC-ESTRO jointly published consensus recommendations in 2020 to standardize CT-IGABT practices across diverse clinical environments. At Homi Bhabha Cancer Hospital and Research Centre, Visakhapatnam, our prior work (RetroLACER Study) demonstrated that CT-based IGABT can achieve outcomes comparable to MR-IGABT, highlighting its feasibility and potential for wider adoption. Building on this foundation, the EMBRACE III-IMPACT Study seeks to evaluate whether CT-IGABT can be systematically and uniformly implemented in a multi-centre setting and to benchmark clinical outcomes against the standards set by MR-IGABT. Study Design: This is a multicentre, prospective, observational study planned to include approximately 1200 participants with locally advanced cervical cancer. All participants will receive standard-of-care treatment, including EBRT, concurrent weekly cisplatin chemotherapy, and brachytherapy with image-guided planning. Objectives: To assess the feasibility of implementing standardized CT-IGABT protocols across diverse clinical environments. To evaluate local control, disease-free survival, and treatment-related toxicity outcomes for CT-IGABT. To compare and benchmark CT-IGABT outcomes with established MR-IGABT benchmarks from prior international studies. Participant Involvement: Participants will undergo standard diagnostic imaging, EBRT with weekly cisplatin, and brachytherapy using CT-based planning. Imaging and treatment data will be collected, anonymized, and submitted to a central database for review. Regular follow-up visits will monitor tumour control and treatment-related side effects. Benefits: Participants receive internationally standardized, quality-assured treatment protocols. Centres gain access to expert review and QA support from international collaborators, potentially improving treatment quality and outcomes. The study supports global efforts to establish CT-IGABT as a cost-effective, accessible alternative to MRI-based IGABT, expanding equitable cancer care access. Risks: The study is observational and involves standard treatment; therefore, risks and costs are comparable to routine cervical cancer care. Confidentiality and Ethics: All data will be anonymized and handled in compliance with ethical and regulatory standards. Participant confidentiality will be strictly maintained. Written informed consent will be obtained before study participation. Significance: By validating standardised CT-based protocols and establishing outcome benchmarks, the study aims to facilitate widespread adoption of IGABT in resource-limited settings, ultimately improving treatment accessibility and survival outcomes.

Conditions

Locally Advanced Cervical Cancer; Brachytherapy; CT; Transrectal Ultrasound

Keywords

Cervical cancer; CT-guided brachytherapy; Image-Guided Adaptive Brachytherapy (IGABT); Locally advanced cervical cancer; Implementation study; Resource-limited settings; Low- and middle-income countries (LMICs); EMBRACE III; Trans-rectal ultrasound during BT; Pre BT MR Imaging

Outcome Measures

Primary Outcomes (1)

• Local control in relation to anatomical compartments and specific BT targets (CTV- THR) and morbidity related to OAR in the pelvis.

  Remission status (complete, partial, stable \& progressive disease) should be evaluated 3 - 6 months after treatment by gynaecological examination and imaging wherever applicable. Regular follow-up including gynaecological examination with planned appointments 6, 9, 12, 18, 24, 30 and 36 months after treatment to be done \& documented. In case of suspected recurrence, biopsy / fine needle aspiration cytology to confirm recurrences and appropriate imaging to be performed at the discretion of treating physician \& Institutional protocol. Physician assessed morbidity will be scored prospectively with the Common Terminology Criteria for Adverse Events (both CTCAE V 5.0) on apriori selected, clinically relevant endpoints related to gastro-intestinal, genito-urinary, vaginal and several unspecific symptoms. Morbidity will be classified into early and late as per standard definition (early being within the first 90 days after completion of treatment).

  36 & 60 Months

Secondary Outcomes (4)

• Regional control

  6, 9, 12, 18, 24, 30 and 36 months

• Progression free survival

  6, 9, 12, 18, 24, 30 and 36 months

• Overall survival

  6, 9, 12, 18, 24, 30 and 36 months

• Morbidity

  6, 9, 12, 18, 24, 30 and 36 months

Study Arms (1)

Cohort A - Advanced CT Environment, Cohort B - Basic CT Environment

COHORT A: Pre Brachytherapy MR to assess the regression of primary tumour after EBRT +/- CT, defining target and pre-planning of BT implantation followed by CT Imaging with BT applicator in place. Alternatively, if Pre-BT MR is not feasible, use of TRUS imaging information during BT application to define the target on CT Imaging with BT applicator in situ COHORT B: CT Imaging with BT Applicator in place-based treatment planning for each BT application.

Other: CT IGABT

Interventions

CT IGABT OTHER

Participants with locally advanced cervical cancer will receive standard-of-care treatment, including external beam radiotherapy (EBRT) with concurrent weekly cisplatin chemotherapy, followed by image-guided adaptive brachytherapy (IGABT). Brachytherapy planning will utilize CT-based imaging to define target volumes and organs at risk according to international consensus guidelines. Centres with advanced imaging capabilities may integrate MRI or transrectal ultrasound (TRUS) for pre-brachytherapy assessment (Cohort A), while others will use CT-only planning (Cohort B). All treatments will follow standardized protocols with centralized quality assurance and data review to evaluate feasibility, consistency, and clinical outcomes of CT-IGABT implementation across diverse clinical environments.

Cohort A - Advanced CT Environment, Cohort B - Basic CT Environment

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Biological females diagnosed with cervical cancer
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study will include approximately 1200 women with histologically confirmed, locally advanced cervical cancer (FIGO stages IB3-IVA) who are planned for curative chemoradiation followed by brachytherapy at the primary treating center. Participants will be recruited from multiple national and international centres equipped with CT-based brachytherapy facilities. All will undergo standardized treatment and follow-up as per study protocol, with imaging and outcome data submitted to a centralized database for quality assurance and analysis.

You may qualify if:

• Cancer of the uterine cervix considered suitable for curative treatment with definitive chemo radiotherapy including brachytherapy.
• Biopsy showing invasive squamous-cell carcinoma or adenocarcinoma or adeno - squamous cell carcinoma of the uterine cervix.
• FIGO (2018) stage IB2 to IVA
• Willingness to participate by signing informed consent form.

You may not qualify if:

• Other previous or current primary malignancies except carcinoma in situ of the cervix.
• Metastatic Inguinal Nodes not amenable to radical radiation therapy
• Metastatic disease in para-aortic region beyond renal vessels
• Not eligible for concurrent cisplatin chemotherapy (creatinine clearance \< 50mg/ml/min)
• Previous pelvic or abdominal radiotherapy.
• Previous total or partial hysterectomy.
• Patients receiving BT alone.
• Patients receiving EBRT alone.
• Patients receiving any form of neoadjuvant anti-neoplastic therapy prior to definitive treatment or adjuvant therapy
• Active infection or severe medical condition which precludes radical chemoradiotherapy.
• Pregnant or lactating or childbearing potential without adequate contraception.

Sponsors & Collaborators

• Homi Bhabha Cancer Hospital & Research Centre: lead
• Medical University of Vienna: collaborator

Study Sites (1)

Homi Bhabha Cancer Hopsital & Research Centre

Visakhapatnam, Andhra Pradesh, 530053, India

Location

Related Publications (7)

• Haie-Meder C, Potter R, Van Limbergen E, Briot E, De Brabandere M, Dimopoulos J, Dumas I, Hellebust TP, Kirisits C, Lang S, Muschitz S, Nevinson J, Nulens A, Petrow P, Wachter-Gerstner N; Gynaecological (GYN) GEC-ESTRO Working Group. 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. Radiother Oncol. 2005 Mar;74(3):235-45. doi: 10.1016/j.radonc.2004.12.015.

  PMID: 15763303 RESULT

• Cibula D, Raspollini MR, Planchamp F, Centeno C, Chargari C, Felix A, Fischerova D, Jahnn-Kuch D, Joly F, Kohler C, Lax S, Lorusso D, Mahantshetty U, Mathevet P, Naik R, Nout RA, Oaknin A, Peccatori F, Persson J, Querleu D, Bernabe SR, Schmid MP, Stepanyan A, Svintsitskyi V, Tamussino K, Zapardiel I, Lindegaard J. ESGO/ESTRO/ESP Guidelines for the management of patients with cervical cancer - Update 2023. Virchows Arch. 2023 Jun;482(6):935-966. doi: 10.1007/s00428-023-03552-3. Epub 2023 May 5.

  PMID: 37145263 RESULT

• Miriyala R, Sreelakshmi KK, Chiriki K, Hajare R, Vadgaonkar R, Nachu S, Grover S, Mahantshetty U. GPP06 Presentation Time: 9: 45 AM: Early Clinical Outcomes of Cervical Cancer Treated with CT Based Image Guided Adaptive Brachytherapy Using IBS-GEC ESTRO-ABS Recommendations. Brachytherapy. 2024 Nov 1;23(6):S19.

  RESULT

• Mahantshetty U, Naga Ch P, Khadanga CR, Gudi S, Chopra S, Gurram L, Jamema S, Ghadi Y, Shrivastava S. A Prospective Comparison of Computed Tomography with Transrectal Ultrasonography Assistance and Magnetic Resonance Imaging-Based Target-Volume Definition During Image Guided Adaptive Brachytherapy for Cervical Cancers. Int J Radiat Oncol Biol Phys. 2018 Dec 1;102(5):1448-1456. doi: 10.1016/j.ijrobp.2018.05.080. Epub 2018 Jun 7.

  PMID: 30146092 RESULT

• Potter R, Tanderup K, Kirisits C, de Leeuw A, Kirchheiner K, Nout R, Tan LT, Haie-Meder C, Mahantshetty U, Segedin B, Hoskin P, Bruheim K, Rai B, Huang F, Van Limbergen E, Schmid M, Nesvacil N, Sturdza A, Fokdal L, Jensen NBK, Georg D, Assenholt M, Seppenwoolde Y, Nomden C, Fortin I, Chopra S, van der Heide U, Rumpold T, Lindegaard JC, Jurgenliemk-Schulz I; EMBRACE Collaborative Group. The EMBRACE II study: The outcome and prospect of two decades of evolution within the GEC-ESTRO GYN working group and the EMBRACE studies. Clin Transl Radiat Oncol. 2018 Jan 11;9:48-60. doi: 10.1016/j.ctro.2018.01.001. eCollection 2018 Feb.

  PMID: 29594251 RESULT

• 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. IBS-GEC ESTRO-ABS recommendations for CT based contouring in image guided adaptive brachytherapy for cervical cancer. Radiother Oncol. 2021 Jul;160:273-284. doi: 10.1016/j.radonc.2021.05.010. Epub 2021 May 18.

  PMID: 34019918 RESULT

• Potter R, Tanderup K, Schmid MP, Jurgenliemk-Schulz I, Haie-Meder C, Fokdal LU, Sturdza AE, Hoskin P, Mahantshetty U, Segedin B, Bruheim K, Huang F, Rai B, Cooper R, van der Steen-Banasik E, Van Limbergen E, Pieters BR, Tan LT, Nout RA, De Leeuw AAC, Ristl R, Petric P, Nesvacil N, Kirchheiner K, Kirisits C, Lindegaard JC; EMBRACE Collaborative Group. MRI-guided adaptive brachytherapy in locally advanced cervical cancer (EMBRACE-I): a multicentre prospective cohort study. Lancet Oncol. 2021 Apr;22(4):538-547. doi: 10.1016/S1470-2045(20)30753-1.

  PMID: 33794207 RESULT

Related Links

• Improving cervical cancer care through personalized radiation therapy PROMISE, IMPACT, and REWIND studies for image-guided adaptive brachytherapy.

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Dr Umesh Mahantshetty, MD, DNB

  HOMI BHABHA CANCER HOSPITAL AND RESEARCH CENTRE

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 17, 2025
• First Posted: November 25, 2025
• Study Start: November 1, 2025
• Primary Completion (Estimated): November 1, 2031
• Study Completion (Estimated): November 1, 2031
• Last Updated: November 25, 2025

Record last verified: 2025-11

Locations

IN (1)