Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02759133 |
| Other study ID # |
2015/18 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
June 2016 |
| Est. completion date |
August 3, 2023 |
Study information
| Verified date |
November 2023 |
| Source |
Centre Antoine Lacassagne |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This is a monocentric, non-inferiority, randomized cohort study with an open 1:1 ratio
comparing the impact of iodine seed tumor localization (arm B) vs. standard localization
using a metal guide (arm A) on the quality of the surgical resection margins in parallel
groups with an interim analysis in patients with breast cancer.
Randomization will be performed using histologic status stratification: in situ ductal
/invasive lobular +/- an in situ component / invasive ductal +/- an in situ component.
Description:
The widespread development of organized breast cancer screening has enabled diagnosis of
nonpalpable, small-size cancer lesions (infraclinical stage). When conservative breast
surgery is scheduled (tumorectomy or zonectomy), preoperative localization of the lesion is
mandatory. To date, wire localization of non-palpable lesions is the most frequently used
technique worldwide.
Nevertheless, this technique presents a number of drawbacks:
- it is very uncomfortable for the patient. The wire is implanted transcutaneously,
crosses the skin to reach the lesion and then protrudes outside the breast, thus
limiting the patient's mobility and giving rise to discomfort and even pain during
movement.
- furthermore, and for the same above-mention reasons, there is a risk of the wire
becoming dislodged, breaking or being disinserted during patient movements (transfer
between units, pre-op shower, installation in the operating room), thus jeopardizing the
quality of the planned surgery by increasing the risk of unhealthy resection margins or
even of non-removal of the tumor. Cases have even been reported of intrapulmonary wire
migration.
- in order to lessen these risks, the wire must be placed as late as possible before
transfer to the surgical wing (the previous day at the earliest). Consequently,
organizing the patient's transfer, particularly in the event of outpatient surgery (less
than 12h at the hospital) becomes complicated and requires coordination between the
different units in charge of preoperative management (radiology, nuclear medicine,
admittance, and operating room) and early inclusion of these patients in the operating
room schedule or postponement of surgery in the event of migration or displacement of
the wire. These various constraints can result in a reduction of the number of patients
able to benefit from outpatient management, as demonstrated by Dravet et al. Several
alternative techniques have been put forward in order to overcome these difficulties,
including radioguided seed localization (RSL), which consists in implanting a sealed
source of radioactive iodine125 (iodine seed) inside the tumor to provide a preoperative
marker which can be monitored by the surgeon using a gamma probe. The RSL technique is
currently used in Europe (Netherlands), Canada and the USA.
This technique appears to offer several advantages:
- It is a simple radiologic technique performed under ultrasound or stereotaxic control,
allowing accurate localization of the lesion with no risk of the marker moving or being
displaced,
- It requires no special training for surgeons already skilled in the use of gamma probes
in the sentinel node technique,
- It allows concomitant, interference-free performance of sentinel node surgery by means
of a gamma probe able to detect specifically Tc99m and/or Iodine 125,
- It is free of organizational localization constraints limiting access to outpatient
surgery, which ranks as a high priority for our governing bodies (50% of all surgeries
will be performed on an outpatient basis by 2016). As the half-life of iodine seeds is
60 days, it should be possible, in theory, to insert them several days, or even several
months, before surgery. In this way, patient transfer is simplified and the turnover of
the operating block for outpatient management can be increased. Moreover, this
localization method could also be used for tumorectomies following neoadjuvant
chemotherapy,
- It presents none of the drawbacks related to patient mobility. Patient comfort is
enhanced and the patient is able to move freely, with fewer risks of displacement or
disinsertion, and less pain, etc.
- Patient satisfaction is higher among those women who have undergone iodine seed
localization as opposed to the conventional localization techniques
Furthermore, various studies have demonstrated the safety of this technique in terms of
radiation protection as radiation is minimal to the patient (equivalent to the amount
received from two mammography views) as well as to the staff. Its reliability regarding the
surgical excision procedure (positive or inadequate margin rates, revision surgery rates) has
been demonstrated in 3 randomized studies with a high level of evidence.
Thus, in 2001, Gray et al. published the first randomized study comparing the RSL technique
with the conventional wire method and showed the superiority of iodine seed localization in
terms of positive margin and surgical revision rates (RSL 26% vs WL 26%, p=0.02) with no
concomitant increase in tumorectomy specimen volumes or marker migration rates. More
recently, Lovrics et al. (2011) and Bloomquist et al (2015) published randomized
non-inferiority studies highlighting the equivalent results between these two techniques
regarding the quality of tumor excision (positive margins rates in: RSL 15.1% vs WL 19%
p=0.389, and in: RSL 19.4% vs 15.3%, p=0.53). In addition, the RSL method showed a
significant advantage regarding operating times and pain experienced by patients during the
localization procedure.
No French team has investigated this localization method on account of legal constraints.
Nonetheless, it would appear that the wire localization technique does not satisfy surgical
teams since another pre-operative localization technique involving injection of Tc99m into
contact with the tumor has been developed over the past few years to replace the wire method.
This procedure has met with little success, and has been gradually abandoned. Unfortunately,
injecting Tc99m around the tumor renders the surgical procedure less precise or necessitates
resecting a large segment of the gland with potentially damaging esthetic repercussions.
Implantation of a sealed radioactive source such as an iodine seed helps mitigate this
drawback.
This study project aims to evaluate the feasibility and safety of using 1 grain of iodine for
localization purposes by means of a randomized comparative study comparing wire localization
with iodine seed localization in patients presenting an in situ, biopsy-proven, non-palpable
invasive or ductal breast carcinoma requiring conservative surgical management associated, or
not, with an axillary procedure (SN removal or axillary curettage).
