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Trial registered on ANZCTR


Registration number
ACTRN12611000667910
Ethics application status
Approved
Date submitted
13/06/2011
Date registered
1/07/2011
Date last updated
30/09/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
PILOT STUDY: I-125 seeds can be safely and accurately used for radioguided occult lesion localisation and removal of impalpable breast cancers ("ROLLIS")
Scientific title
PILOT STUDY: I-125 seeds can be safely and accurately used for radioguided occult lesion localisation and removal of impalpable breast cancers ("ROLLIS")
Secondary ID [1] 262482 0
Nil
Universal Trial Number (UTN)
U1111-1121-8082
Trial acronym
ROLLIS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
breast cancer 267971 0
Condition category
Condition code
Cancer 268101 268101 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The "seed" consists of a small titanium capsule which contains a small quantity of very low dose radioactivity in the form of the radioisotope Iodine 125 (I-125). The I-125 is in a solid state within the seed, covalently bound to a silver wire. The seed is placed in the breast within or next to the abnormal area by the radiologist, using ultrasound or stereotactic mammographic guidance. The Iodine 125 within the seed emits a low energy gamma photon which is detected by the surgeon in theatre, using a hand held gamma probe. The gamma probe makes a noise, the volume of which is proportional to the amount of signal that it picks up from the seed. The highest number of counts (maximum noise) corresponds to the location of the seed and therefore the abnormal area in the breast. The probe is very directionally sensitive and is used by the surgeon to not only make his/her incision in the optimal position relative to the abnormal area but also to assist them to remove the abnormality together with a small surrounding cuff of normal tissue.
All participants will also have the standard localisation method, which is the insertion of a hook-wire as a "back-up" during the introduction of this new technique.
Intervention code [1] 266658 0
Treatment: Surgery
Intervention code [2] 266661 0
Treatment: Devices
Comparator / control treatment
Not applicable
Control group
Uncontrolled

Outcomes
Primary outcome [1] 266850 0
successful removal of the impalpable breast cancers that have been localised using the I 125 seed
Timepoint [1] 266850 0
assessed at time of pathology review of specimen the next working day after surgery, pathologist describes lesion as being present
Primary outcome [2] 266851 0
successful removal of I-125 seeds inserted for lesion localisation and return to physicist for safe storage
Timepoint [2] 266851 0
assessed at time of surgery by finding high count levels within specimen using gamma probe, visualisation of seed within specimen on specimen radiograph, seed returned to physicist after removal by pathologist on the day of specimen processing
Secondary outcome [1] 276502 0
Radiologist, surgeon and pathologist gain expertise in using this technique
Timepoint [1] 276502 0
assessed by review of questionnaires relating to ease of performing the procedure on the day of surgery

Eligibility
Key inclusion criteria
Women aged over 40 years with good life expectancy
A signed and dated written informed consent is obtained prior to participation
Histologically confirmed invasive or in situ breast carcinoma
Non-palpable breast tumour
Single lesion
Candidate for breast conserving surgery (BCS) based on clinical and radiologic evaluation
Minimum age
40 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Male patient
Female, age less than 40 years
Pregnancy or lactation
Periareolar lesion
Contraindication to breast conserving surgery
Surgery after 4pm
Nuclear Medicine or PET radioisotope administration that may adversely affect the procedure

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Eligible women will be given a patient information sheet and invited to participate in the trial by their surgeon.
All participants will have the standard localisation procedure as well as the new method of localistion performed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 6754 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [2] 6755 0
Royal Perth Hospital - Perth
Recruitment hospital [3] 6756 0
St John of God Hospital, Subiaco - Subiaco
Recruitment postcode(s) [1] 14398 0
6009 - Nedlands
Recruitment postcode(s) [2] 14399 0
6000 - Perth
Recruitment postcode(s) [3] 14400 0
6008 - Subiaco

Funding & Sponsors
Funding source category [1] 267307 0
Self funded/Unfunded
Name [1] 267307 0
Address [1] 267307 0
Country [1] 267307 0
Australia
Primary sponsor type
Hospital
Name
Sir Charles Gairdner Hospital
Address
Verdun Street
Nedlands
WA 6009
Country
Australia
Secondary sponsor category [1] 266224 0
Hospital
Name [1] 266224 0
Royal Perth Hospital
Address [1] 266224 0
Wellington Street
Perth
WA 6001
Country [1] 266224 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 269142 0
Sir Charles Gairdner Hospital Human Research Ethics Committee
Ethics committee address [1] 269142 0
Level 2, A Block, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands WA 6009
Ethics committee country [1] 269142 0
Australia
Date submitted for ethics approval [1] 269142 0
Approval date [1] 269142 0
15/04/2011
Ethics approval number [1] 269142 0
2011-025
Ethics committee name [2] 269143 0
Royal Perth Hospital Human Research Ethics Committee
Ethics committee address [2] 269143 0
Level 5, Colonial House, Royal Perth Hospital, GPO Box 2212, Perth, WA 601
Ethics committee country [2] 269143 0
Australia
Date submitted for ethics approval [2] 269143 0
Approval date [2] 269143 0
12/05/2011
Ethics approval number [2] 269143 0
2011.007
Ethics committee name [3] 296055 0
St John of God Health Care Ethics Committee
Ethics committee address [3] 296055 0
Level 3, St John of God House, 177-179 Cambridge St, WEMBLEY WA 6014
Ethics committee country [3] 296055 0
Australia
Date submitted for ethics approval [3] 296055 0
07/01/2015
Approval date [3] 296055 0
29/05/2014
Ethics approval number [3] 296055 0
672

Summary
Brief summary
When a cancer needs to be removed after a biopsy (and the surgeon cannot feel it) it is normally localised and marked for the surgeon by a radiologist who places a fine wire into the abnormality using ultrasound or x-ray guidance, sterile conditions and after using local anaesthetic (to numb the area). This “wire localization procedure” is done on the day of the operation and has been the standard treatment used at this hospital for over 20 years.
A gentle mammogram picture is necessary to check the position of the wire. The surgeon uses the wire to guide them during the operation and the abnormality and the wire are removed whilst you are asleep.

The localization procedure can be difficult and time consuming. Sometimes the wire can be difficult to put in, especially if the breast tissue is very firm. Occasionally the tip of the wire is not right next to the abnormality which means that another wire needs to be put in.
The direction the Radiologist has to take to place the wire may not give the best approach for the surgeon and the incision may be some distance from the abnormality. Sometimes after the pathologist has looked at the removed tissue, it is found that the abnormality has not been completely removed, which means that a further operation is needed to make sure all the abnormal tissue has been removed.

More recently surgeons overseas have been using an alternative way of marking small breast abnormalities using a low dose radioactive “seed” which contains Iodine 125. This is placed into or next to the abnormality either on the day before or the day of the surgery. The surgeon then uses a special hand held probe that can detect the signal given out by the seed to find the abnormal area within the breast. The probe makes a noise which becomes louder the closer it is to the abnormality and gives continuous feed back to the surgeon so that they can adjust their position and to help make sure as much of the abnormal area as possible is removed during the one operation.
Studies suggest that with this technique the abnormality is more often completely removed without the need for a further operation and because it is easier for the surgeon to find the abnormality, the appearances of the breast after the operation may be better than if a wire localization of the lesion had been performed.

The technique of inserting the radioactive seed and removing it is reported to be very easy with very few complications.
Our surgeons are already trained in the technique of using the special hand held probe to find and remove lymph glands after the injection of a radioactive liquid and have been doing this for many years (sentinel lymph node removal). The use of the probe for detecting and removing the seed will be a similar technique.
Our radiologists are also already very experienced in placing small metallic markers (similar to the seeds apart from being non radioactive) into the breast after biopsying small abnormalities.

For the 20 participants in this study, we are planning to use the standard wire localization as well as placing a radioactive seed into the breast abnormality to enable us to gain experience with the new technique. The wire will be there as a backup to make sure your abnormality is removed

We will review our results at the end of the study to see if we had any problems with the new technique that we need to improve on. If, as we anticipate there are no problems, we plan to start a large research trial to compare the results of surgery using the seeds compared with the wire to localize small breast cancers.
Trial website
Trial related presentations / publications
Publications:
- Taylor DB, Bourke AG, Hobbs MM, Dixon G, Phillips M, Saunders CM. (In press). Breast localization techniques and margin definitions used by Australian and New Zealand surgeons. ANZ Journal of Surgery. http://dx.doi.org/10.1111/ans.13632
- Bourke AG, Taylor DB, Westcott E, Hobbs M, Saunders C. (2016). Iodine-125 seeds to guide removal of impalpable breast lesions: radio-guided occult lesions localization – a pilot study. ANZ Journal of Surgery. http://dx.doi.org/10.1111/ans.13460
- Ballal H, Taylor DB, Bourke AG, Latham B, Saunders CM. (2015). Predictors of re-excision in wire-guided wide local excision for early breast cancer: a Western Australian multi-centre experience. ANZ Journal of Surgery. 85(7-8). 540-5. http://dx.doi.org/10.1111/ans.13067
- Taylor DB, Bourke AG, Westcott E, Burrage J, Latham B, Riley P, et al. (2015). Radioguided occult lesion localisation using iodine-125 seeds ('ROLLIS') for removal of impalpable breast lesions: First Australian experience. J Med Imaging Radiat Oncol. http://dx.doi.org/10.1111/1754-9485.12302
- Dissanayake S, Dissanayake D, Taylor D. (2015). Radio-guided occult lesion localisation using iodine 125 Seeds “ROLLIS” to guide surgical removal of an impalpable posterior chest wall melanoma metastasis. J Med Radiat Sci. 62(3), 230–3. http://dx.doi.org/10.1002/jmrs.125
- Dessauvagie BF, Frost FA, Sterrett GF, Hardie M, Parry J, Latham B, Taylor D, et al. (2015). Handling of radioactive seed localisation breast specimens in the histopathology laboratory: the Western Australian experience. Pathology. 47(1), 21-6. http://dx.doi.org/10.1097/PAT.0000000000000197
- Jackson L, Bourke AG, Abdul Aziz F, Taylor D. (2014) Radioactive seed localisation to guide removal of impalpable lymph nodes (Radioguided Occult Lesion Localisation using Iodine-125 seeds, "ROLLIS"). BMJ Case Rep. http://dx.doi.org/10.1136/bcr-2013-203267
Letter to the editor:
- Taylor D, Landman J. ‘Rolling out radioguided occult lesion localisation for breast tumours’: moving from ROLL to ROLLIS. (2015). Journal of Medical Radiation Sciences. 62(2):175-6. http://dx.doi.org/10.1002/jmrs.109
Poster presentations:
- Bourke A, Taylor D, Latham B, Saunders C, et al. Radioguided Occult Lesion Localisation using Iodine-125 (I-125) seeds: a simple, safe and effective technique to guide surgical removal of impalpable breast lesions: the ROLLIS Pilot Extension Study (RPES). 2014 Combined Scientific Meeting: Imaging and Radiation in Personalised Medicine; 4-7 Sep 2014; Melbourne Convention and Exhibition Centre. RANZCR; 2014: R-0073.
- Riley PJ, Bourke AG, Taylor D, Westcott E, Jose C, Ballal H, et al. Steps to success with ROLLIS: how to commence using Radioguided Occult Lesion Localisation with I-125 seeds for removal of impalpable breast lesions (Poster Presentation). European Congress of Radiology 2012.
- Taylor D, Bourke A, Hobbs M, Dixon G, Phillips M, Saunders C. How do ANZ surgeons localise impalpable cancers? 2014 Australasian Breast Congress.
- Taylor D, Bourke A, Hobbs M, Dixon G, Saunders C. Evaluation of methods used to guide breast conserving surgery by Australian and New Zealand breast surgeons. Australasian Breast Congress; 9-11 Oct 2014; Gold Coast, Australia.
Oral presentations and workshops:
- Bourke AG et al. New localisation tools – Radioguided-Occult Lesion Localisation using 125-Iodine Seeds (ROLLIS) Breast Lesions. Scientific Meeting of the Graduates of Royal College of Surgeons in Ireland, 27th August 2015.
- Bourke AG et al. “ROLLIS” Radioguided Occult Lesion Localisation using Iodine-125 (I-125) Seeds for removal of impalpable breast lesions: first Australian results. Symposium Cancer Council WA Nov 2014.
- Taylor D. Radioguided Occult Lesion Localisation using Iodine 125 Seeds for removal of impalpable breast lesions, first Australian results” (Recipient of the award for best oral presentation) Australasian Breast Congress, Australasian Society for Breast Diseases and BreastSurgANZ Society Meeting, Gold Coast, 9-11 October 2014.
Public notes

Contacts
Principal investigator
Name 32667 0
Dr Anita Bourke
Address 32667 0
Breast Centre, G Block 1st Floor
Sir Charles Gairdner Hospital
Hospital Ave
Nedlands WA 6009
Country 32667 0
Australia
Phone 32667 0
+18 6547 2233
Fax 32667 0
Email 32667 0
anita.bourke@health.wa.gov.au
Contact person for public queries
Name 15914 0
Dr Dr Donna Taylor
Address 15914 0
Department of Diagnostic and Interventional Radiology
Royal Perth Hospital
PO Box X2213
GPO Perth 6001
Country 15914 0
Australia
Phone 15914 0
61 8 92242125
Fax 15914 0
61 8 92243764
Email 15914 0
donna.taylor@health.wa.gov.au
Contact person for scientific queries
Name 6842 0
Dr Dr Donna Taylor
Address 6842 0
As above
Country 6842 0
Australia
Phone 6842 0
61 8 92242125
Fax 6842 0
61 8 92243764
Email 6842 0
donna.taylor@health.wa.gov.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary