Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Breast Neoplasms

Recurrence

Breast Diseases

Skin Diseases

The experimental policy is to give targeted intra-operative radiotherapy (TARGIT-Boost) in a single dose to substitute for the usual boost dose, in addition to whole breast external beam radiotherapy delivered according to local treatment guidelines.

The conventional policy is to receive radiation boost to the tumour bed delivered by external beam radiotherapy (EBRT) in addition to whole breast external beam radiotherapy delivered according to local treatment guidelines.

Boost to the tumour bed, with whole breast EBRT delivered according to local policy.

Boost to the tumour bed

Norman R Williams, PhD

Nick Roberts

Alexandra Banks

Dennis R Holmes, MD

Blerina Pople

Nayana Dekhne, MD

Pamela Stephenson

Benjamin T Gielda

Pond Kelemen, MD

Courtney Yanda

Stephanie Valente

Cortney Montgomery

Geraldine Jacobson

Corinne Zipperer, RN

William Owens

Xinguang Wang

Tao Ouyang

Christel Breton-Callu, MD

Boly Ann

Serge Danhier, MD

Etienne Martin, MD

Christelle Faure, MD

Didier Cowen, MD

Magali Le Blanc, MD

Francoise Izar, MD

Samuele Massarut, MD

Fabiana Gregucci

Fernando Bozza

Sung Gwe Ahn

Joon Jeong

Zarinah Abdul Rahman

Nur Aishah Mohd Taib

Maha Abdel Hadi

Kyara Bergstrom

Carol Benn

Yastira Ramdas

Montse Ventura

Evelyn Martínez Pérez

Pedro C Lara, MD

Bärbel Papassotiropoulos

Sikrit Denariyakoon

Adhisabandh Chulakadabba

Julian Singer, MD

Jayant S Vaidya, MBBS FRCS

Mo Keshtgar, MB BS

Sweta Sethi

Michael Douek

Nathan Coombs, MB BS

Elizabeth Happle

Sanjay Raj

TARGIT-Boost is an international randomised clinical trial designed to test the hypothesis that the tumour bed boost delivered as a single dose of targeted intraoperative radiotherapy (TARGIT-B) is superior to the conventional course of external beam radiotherapy boost (EBRT-Boost), especially in women with high risk of local recurrence. It is a pragmatic trial in which each participating centre can use the local predefined inclusion/exclusion criteria for entry into the trial. Only centres with access to the Intrabeam® (Carl Zeiss) are eligible to enter patients into the trial.

Eligible patients are those with a higher risk of local recurrence after breast conserving surgery.

After giving consent patients are randomised to either TARGIT Boost or EBRT Boost. All patients will receive whole breast EBRT. They may receive any other adjuvant treatments as deemed necessary. The protocol recommends that patients be followed at six monthly intervals for three years and then annually.

The primary endpoint is ipsilateral breast recurrence rate. Secondary endpoints are relapse-free survival, site of recurrence, overall survival (breast-cancer specific and non-breast cancer deaths) patient satisfaction and quality of life.

DESIGN: A pragmatic multi-centre randomised clinical trial to test whether TARGeted Intraoperative radioTherapy as a tumour bed Boost (TARGIT-B) is superior in terms of local relapse within the treated breast compared with standard post-operative external beam radiotherapy boost in women undergoing breast conserving therapy who have a higher risk of local recurrence. Patients can be entered before the primary surgery or in a smaller proportion of cases, post-pathology. SETTING: Specialist breast units in UK, USA, Canada, Australia and Europe; 31 centres currently recruiting in the TARGIT-A trial and several are ready to join. TARGET POPULATION: Breast cancer patients suitable for breast conserving surgery, but with a high risk of local recurrence. Details of inclusion and exclusion are given in part 2. Briefly the patients should be either younger than 45 or if older, need to have certain pathological features that confer a high risk of local recurrence of breast cancer. HEALTH TECHNOLOGIES BEING ASSESSED. The TARGIT Technique: The Intrabeam® (Carl Zeiss, FDA approved and CE marked) is a miniature electron beam-driven source which provides a point source of low energy X-rays (50kV maximum) at the tip of a 3.2mm diameter tube. The radiation source is inserted into the tumour bed immediately after excision of the tumour and switched on for 20-35 minutes to provide intra-operative radiotherapy accurately targeted to the tissues that are at highest risk of local recurrence. The physics, dosimetry and early clinical applications of this soft x-ray device have been well studied. For use in the breast, the technique was first developed and piloted at University College London. The radiation source is surrounded by a spherical applicator, specially designed (and available in various sizes) to produce a uniform field of radiation at its surface, enabling delivery of an accurately calculated dose to a prescribed depth. It is inserted in the tumour bed and apposed to it with surgical sutures and/or other means. As the x-rays rapidly attenuate the dose to more distant tissues is reduced; this also allows it to be used in standard operating theatres. 20 Gy is delivered to the tumour bed surface in 20-35 minutes, after which the radiation is switched off, the applicator removed, and the wound closed in the normal way. This simple technique has potentially several advantages over convential external beam radiotherapy, interstitial implantation of radioactive wires or conformal external beam radiotherapy. The first pilot of twenty-five cases was at performed at UCL using TARGIT technique as a replacement for the boost dose of radiotherapy; full dose external beam treatment was subsequently given. The phase II study of 300 patients was published and recently updated with long term data along with favourable toxicity and cosmetic outcome results of individual cohorts. A mathematical model of TARGIT developed recently (funded by Cancer Research UK) suggests that it could be superior to conventional radiotherapy. Translational research has found that TARGIT impairs the surgical-trauma-stimulated proliferation and invasiveness of breast cancer cells. This effect of radiotherapy may act synergistically with its tumouricidal effect yielding a superior result. MEASUREMENT OF COST AND OUTCOME: Patient assessments will be clinical examination (6 monthly x 3 years then yearly x 10 years) and mammography (yearly). with ulstrasound (if needed) . Primary outcome: histologically/cytologically proven local recurrence. Secondary: site of relapse in the breast, overall survival, local toxicity (RTOG and LENT SOMA criteria), cosmesis, quality of life, patient satisfaction and health economics. The cost and cost-effectiveness of TARGIT versus EBRT, both as boost, will be calculated from a NHS and personal social services (PSS) perspective. Costs directly incurred by patients will also be assesed, since EBRT as a boost is likely to impose additional time and travel expense to patients and families.

A Comparison of Intra-operative Radiotherapy Boost With External Beam Radiotherapy Boost in Early Breast Cancer.

An International Randomised Controlled Trial to Compare Targeted Intra-operative Radiotherapy Boost With Conventional External Beam Radiotherapy Boost After Lumpectomy for Breast Cancer in Women With a High Risk of Local Recurrence.

To evaluate whether a tumour bed boost in the form of a single fraction of radiotherapy given intra-operatively and targeted to the tissues at the highest risk of local recurrence is superior (in terms of local tumour control) to standard post-operative external beam radiotherapy boost, after breast conserving surgery in women undergoing breast conserving therapy who have a higher risk of local recurrence.

Site of relapse within the breast will be recorded in order to assess whether the recurrence is at the site of the initial tumour or at a new site and whether it has occurred within the treated field (TARGIT or EBRT boost).

Relapse-free survival will be recorded as the time interval between randomisation and the date of confirmation of recurrence. The actual date to be used is the clinic day on which the investigations that led to a confirmed diagnosis of the recurrence were requested. Relapse-free survival will include any recurrence of breast cancer or death without a prior report of relapse.

Overall survival will be the time interval between randomisation and death.

Local toxicity and morbidity will be recorded as adverse events related to the primary treatment of the breast cancer. Quality of life will be assessed though validated patient-completed questionnaires.

The primary patient reported outcome endpoint for quality of life will be the FACT-B+4 trial outcome index (TOI) score. The TOI score (0-180) is a sum of the scores of the 27 items included in the physical well-being, functional well-being and breast cancer subscales of the FACT-B+4. A change of at least 5 points in TOI is considered to be clinically relevant or a minimally important difference (Eton et al. 2004). Secondary endpoints will be: 1) the five item arm functioning subscale score (0-20) 2) The 40 item FACT B+4 score (0-160), which reflects global quality of life including social and emotional well-being.

National Institute for Health Research, United Kingdom

University College, London

Carcinoma

A single fraction of radiotherapy given intra-operatively and targeted to the tissues at the highest risk of local recurrence.

A dose of 20 Gy at the surface of the applicator or 6 Gy at 1cm (in water) is prescribed by the radiation oncologist and delivered to the breast tissue. This takes approximately 30 minutes, depending on the size of the applicator.

Intrabeam

All patients randomised to receive conventional radiotherapy within this trial should be treated in accordance with a pre-specified policy. Dosage should only be applied to the breast; axillary, supra-clavicular and internal mammary nodes should not generally be irradiated by discrete fields.

Post-operative radiotherapy

Jeffrey S Tobias, MD FRCP FRCR

The purpose of this study is to evaluate whether a single fraction of radiotherapy given intra-operatively and targeted to the tissues at the highest risk of local recurrence is equivalent to standard post-operative external beam radiotherapy after breast conserving surgery in women with early stage breast cancer in terms of local relapse within the treated breast.

TARGIT is an international randomised clinical trial designed to test the hypothesis that the strategy of delivering a single dose of targeted intraoperative radiotherapy (IORT) in patients eligible for breast conserving therapy (with the addition of whole breast radiotherapy in those patients at high risk of recurrence elsewhere in the breast \[e.g. lobular carcinomas and extensive intraductal component\]) is equivalent to a conventional course of post-operative external beam radiotherapy (EBRT). The primary endpoints are local and loco-regional recurrence rates. It is a pragmatic trial in which each participating centre has the option to define more restrictive entry criteria than in the core protocol. Only centres with access to the Intrabeam® (Carl Zeiss) enter patients into the trial. Eligible patients are those with tumours of good prognosis suitable for breast conserving surgery. After giving consent patients are randomised to either IORT or to EBRT. They may receive any other adjuvant treatments as deemed necessary, except for neoadjuvant therapy. The protocol requires that patients be followed at six monthly intervals for five years and then annually.

Comparison of Intra-operative Radiotherapy With Post-operative Radiotherapy for Women With Early Breast Cancer

TARGIT: A Randomised Controlled Trial to Compare Targeted Intra-operative Radiotherapy With Conventional Post-operative Radiotherapy After Conservative Breast Surgery for Women With Early Stage Breast Cancer

Carcinoma, Ductal

Carcinoma in Situ

Breast Carcinoma In Situ

Carcinoma, Intraductal, Noninfiltrating

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Patients just accept nipple-sparing mastectomy (NSM) without radiotherapy.

Followed by nipple-sparing mastectomy (NSM),INTRABEAM IORT was carried out with a single dose of 16 Gy for nipple-areola complex (NAC).

Boost with 16 Gy during NSM for nipple-areola complex (NAC)

INTRABEAM (Carl Zeiss, Oberkochen, Germany)

Liao Ning, MD,PhD

Wen LingZhu

The role of NSM is still controversial, mainly because of concern about the oncologic safety of the nipple-areola complex (NAC).INTRABEAM (Carl Zeiss, Oberkochen, Germany) is the most widely used mobile intraoperative radiotherapy (IORT) device to date. This study aims to assess the value of the INTRABEAM system for breast cancer.

Despite the advancement and increasing use of nipple-sparing mastectomy (NSM) is still carried out in a portion of breast cancer patients. However, the role of NSM is still controversial, mainly because of concern about the oncologic safety of the nipple-areola complex (NAC). Radiation therapy uses high-energy x-rays to damage tumor cells. Giving radiation during surgery followed by external-beam radiation to the entire breast may kill more tumor cells.INTRABEAM (Carl Zeiss, Oberkochen, Germany) is the most widely used mobile intraoperative radiotherapy (IORT) device to date. This study aims to broaden the application of the INTRABEAM system for breast cancer, investigating the feasibility of INTRABEAM IORT in NSM with breast reconstruction.

Intra-operative Radiotherapy For Breast Cancer Women After NSM

Intra-operative Radiotherapy For Women With Ductal Carcinoma in Situ Breast Cancer After Nipple-sparing Mastectomy

Within 5 years after surgery,we should evaluate ipsilateral breast tumor recurrence and Disease free survival as the most important outcome measure

Within 5 years after adjuvant chemotherapy,we should evaluateDisease free survival(DFS) rates as thet important outcome measure.

After surgery,we should evaluate overall survival (OR)rates as the secondary important outcome measure.

Liao Ning

MD,PhD

Nervous System Diseases

Neoplasm Metastasis

Brain Neoplasms

Neoplastic Processes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

To determine the efficiency and safety of IORT with low-energy photons to the cavity after resection of brain metastases

Intraoperative radiotherapy application immediately following resection of brain metastases.

Intraoperative radiotherapy

Palmira Foro Arnalot, MD, PhD

Gloria Villalba, MD, PhD

Intraoperative radiotherapy (IORT) is a new alternative for local radiotherapy with the advantages of dose escalation, reduced overall treatment time, and enhanced patient convenience, however the degree of efficacy is unknown, as well as and which is the most efficient dose.

The objective of this study is to evaluate the efficacy and safety of IORT in patients with surgical excision of brain metastases at a dose of 20 Gy is at least as effective and safe as other forms of radiation therapy in patients with resection of brain metastases.

1. INTRODUCTION

   Brain metastases occur in roughly 30% of all cancer patients during their course of disease. Their incidence is believed to rise due to the aging population that develops more cancer per se, an increase in overall survival due to more effective extracranial therapies but with only few (novel) substances crossing the blood-brain barrier and more broadly available and more advanced imaging techniques.

   Neurosurgical treatment remains a cornerstone in the management of brain metastasis, especially for lesions causing mass effects or neurological deficits or in case tissue is necessary to establish a diagnosis. As local recurrence rates are as high as 50-60% after surgical resection alone, adjuvant therapies to prevent such are necessary.

   Whole brain radiotherapy (WBRT) does not influence survival but rather impairs neurocognitive functions and, as histologic in-depth exams of cavity borders showed that most brain metastases infiltrate only 0.3-1.2 mm into the surrounding healthy brain tissue, therefore treatment is to date usually confined to the cavity margin. Thus, the currently recommended standard of care is post-operative stereotactic radiosurgery (SRS) to the resection cavity. One of the drawbacks of this modality is the incidence of radionecrosis, especially in large tumor volumes. As an alternative to radiosurgery, hypofractionated local radiotherapy is also used, reducing the risk of radionecrosis in large volumes. There are no prospective randomized studies comparing both techniques.

   The need to find a modality of radiotherapy that achieves al least the efficacy of radiosurgery or hypofractionated local radiotherapy, without the disadvantages thereof, makes IORT as a possible treatment alternative.

   The objective of this study is to evaluate the efficacy and safety of IORT in patients with surgical excision of brain metastases at a dose of 20 Gy is at least as effective and safe as other forms of radiation therapy in patients with resection of brain metastases.
2. OBJECTIVES

   Primary Objective
   * Median local progression free survival (lPFS), defined as time span (in months) between surgery and recurrence within a 0,5 cm margin around the resection cavity, assessed by serial MRI scans and RANO response assessment criteria for brain metastases .
   * Radiation-related (acute / late) neurotoxicity, assessed by regular neurological examinations and serial MRI scans.

   Secondary objectives
   * Median regional PFS (rPFS), resembling the time (in months) from surgery to any progression outside of the 0,5 cm margin around the resection cavity, assessed by serial MRI scans and RANO response assessment criteria for brain metastases .
   * Global PFS (gPFS), defined as the time (in months) from surgery to any intra- and extracranial tumor progress.
   * Median overall survival (OS), defined as the time (in months) from surgery of brain metastases to death from by any cause.
3. DESIGN

This trial is an open, single arm, single institution, prospective trial to determine the efficiency and safety of IORT with low-energy photons to the cavity after resection of brain metastases. A total of 25 patients will be included.

Intraoperative Radiotherapy in Patients With Brain Metastases

Recurrence within a 0.5 cm margin around the resection cavity, assessed by serial magnetic resonance imaging (MRI scans) and response assessment criteria in neuro-oncology (RANO)

Neurotoxicity related to radiotherapy evaluated according to the scale of the Common Terminology Criteria for Adverse Events (CTCAE) version 5. Score from 0 to 5, with 5 being the worst toxicity

- Acute toxicity: cerebral edema

Neurotoxicity related to radiotherapy evaluated according to the scale of the Common Terminology Criteria for Adverse Events (CTCAE) version 5. Score from 0 to 5, with 5 being the worst toxicity

- Late toxicity: radionecrosis.

To any progression outside of the 0.5 cm margin around the resection cavity, assessed by serial MRI scans and RANO response assessment in neuro-oncology .

The time (in months) from surgery to any intra- and extracranial tumor progress

The time (in months) from surgery of brain metastases to death from by any cause.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Comparison of Intra-operative Radiotherapy Boost With External Beam Radiotherapy Boost in Early Breast Cancer.	NCT01792726	Early Breast Ca...	Boost to the tu...	-	University College, London
A Comparison of Intra-operative Radiotherapy Boost With External Beam Radiotherapy Boost in Early Breast Cancer.	NCT01792726	Early Breast Ca...	Boost to the tu...	-	University College, London
Comparison of Intra-operative Radiotherapy With Post-operative Radiotherapy for Women With Early Breast Cancer	NCT00983684	Invasive Breast... Breast Cancer	Intrabeam Post-operative ...	45 Years -	University College, London
Intra-operative Radiotherapy For Breast Cancer Women After NSM	NCT02389686	Breast Neoplasm...	INTRABEAM (Carl...	17 Years - 80 Years	Guangdong Academy of Medical Sciences
Intraoperative Radiotherapy in Patients With Brain Metastases	NCT04847284	Brain Metastase...	Intraoperative ...	18 Years -	Parc de Salut Mar
Intraoperative Radiotherapy in Patients With Brain Metastases	NCT04847284	Brain Metastase...	Intraoperative ...	18 Years -	Parc de Salut Mar
Intra-operative Radiotherapy For Breast Cancer Women After NSM	NCT02389686	Breast Neoplasm...	INTRABEAM (Carl...	17 Years - 80 Years	Guangdong Academy of Medical Sciences

Spots Global Cancer Trial Database for intrabeam

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Spots Global Cancer Trial Database for intrabeam

Every month we try and update this database with for intrabeam cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for intrabeam cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.