Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT01279304 |
| Other study ID # |
10-04-10/02 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 2011 |
| Est. completion date |
December 2017 |
Study information
| Verified date |
February 2014 |
| Source |
Maastricht Radiation Oncology |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The primary aim of the study is to evaluate the 5 yr locoregional recurrence rate (LRR) in
cT1-2cN0-1(cytology/histology and/or positive SN, excluding patients with > 3 pathologic
axillary nodes on imaging) breast cancer patients, treated with neoadjuvant chemotherapy,
breast surgery, and radiotherapy that is protocolized based on the pathology findings after
chemotherapy and definitive surgery (ypTNM stage).
Description:
Primary systemic treatment for breast cancer patients used to be given only to patients with
locally advanced disease. Although until now no studies have been reported that primary
systemic treatment leads to a superior survival compared to adjuvant chemotherapy [Mauri et
al, 2005; Mieog et al, 2007], the last years have been showing an increase in the use of
primary systemic treatment , also for patients with earlier stages of breast cancer. The
suggested advantages of this policy are 1) that primary systemic treatment allows for
monitoring of the response on the treatment, such that the type of chemotherapy can be
changed in case of no response, and 2) that primary systemic treatment may shrink the tumour
volume, allowing for a higher percentage of breast conserving therapy [Mieog et al, 2007];
and 3) the overall 40% chance of converting positive axillary nodes pre-PST to negative,
questioning the need for an axillary dissection [Fontein et al, 2013; Kuehn et al, 2013]. A
major disadvantage of primary systemic treatment is however, that the indications for
post-operative radiotherapy are based upon studies where loco-regional recurrences were
correlated to the pathological T and N stage in patients who had not been treated with
chemotherapy before surgery. Since primary systemic treatment is affecting the pathological T
and N stage, the indications for post-operative radiotherapy in these patients have become
uncertain.
Objective: The primary aim of the study is to evaluate the 5 yr locoregional recurrence rate
(LRR) in cT1-2cN0-1(cytology/histology and/or positive SN, excluding patients with > 3
pathologic axillary nodes on imaging) breast cancer patients, treated with neoadjuvant
chemotherapy, breast surgery, and radiotherapy that is protocolized based on the pathology
findings after chemotherapy and definitive surgery (ypTNM stage). The secondary aim is to
develop a risk model based on risk factors, that can be used to predict which of the patients
with a cT1-2cN0-1 breast carcinoma, treated with neoadjuvant chemotherapy and surgery, have a
5 yr LRR > 8 % if radiotherapy is withheld.
Study design: This study is a multicentre prospective cohort study. Study population: In
total 710 patients with cT1-2pN0-1, excluding ≥cN2 and patients with > 3 pathologic axillary
nodes on imaging, breast cancer, treated with at least three cycles of chemotherapy followed
by breast and axillary surgery are eligible for the study.
During 5 years (2011-2015) patients diagnosed for primary breast cancer and eligible
according to the criteria will be registered by the National Cancer Registry in this project.
Currently, three surgical strategies are being followed in cT1-2N0-1 patients, treated with
primary systemic treatment :
1. A full axillary lymph node dissection is performed after the primary systemic treatment
, OR
2. A sentinel node procedure is carried out prior to neoadjuvant treatment, and no further
axillary surgery is performed after chemotherapy, if the patient is clinically node
negative (ycN0)), OR
3. A sentinel node procedure is carried out only after primary systemic treatment , in case
patient is still/has become clinically node negative (ycN0).
For all three above mentioned strategies, patients are divided into three risk groups, mainly
based on the post chemotherapy pathological nodal status (strategy 1 and 3), and on the
pre-chemotherapy pathological nodal status and ycN0 status (strategy 2). In addition, for all
three strategies the cT and the ycT status are taken into account to choose the recommended
guideline.
The radiation treatment guidelines for the subsequent three risk groups consist of:
1. Group I - low risk (N = 237):
1. after MRM: no radiotherapy
2. after BCT: radiation treatment of the breast with boost (optional)
2. Group II - intermediate risk (N = 237):
1. after MRM: radiation treatment of the thoracic wall
2. after BCT: radiation treatment of the breast with boost (optional)
3. if no full ALND is performed: add radiation treatment to level 1 and 2
3. Group III - high risk group(N = 237):
1. after MRM: radiation treatment of the thoracic wall and supraclavicular nodes
2. after BCT: radiation treatment of the breast with boost (optional), and
supraclavicular nodes
3. if no full ALND is performed (not recommended): add radiation treatment to the
axilla level 1 and 2 RT of the axillary (after ALND) and internal mammary chain
nodes is optional for group III, based on the local protocol. In case of a positive
sentinel node in the internal mammary chain prior to chemotherapy, internal mammary
chain irradiation is strongly recommended Main study parameters/endpoints: The
primary endpoint is the 5 yr locoregional recurrence rate (LRR). Secondary
endpoints are 10 year LRR, 5, 10, and 15 yr relapse free survival rates (all events
except lost to follow-up, invasive contralateral cancer, and secondary primary
(non-breast) invasive cancer) and overall survival rates. In addition, analyses
will be performed to investigate whether pre-radiotherapy factors (e.g. like age <
40 yr, response to chemotherapy, tumour size) can be identified that correlate with
a high LRR.
Nature and extent of the burden and risks associated with participation, benefit and group
relatedness: Currently no clear data are present in literature showing the indications for
radiotherapy in this patient group. Based on literature that is available for patients
treated with chemotherapy after surgery we have chosen what we think might be the optimal
treatment from a benefit/risk perspective. The study focuses on adequate registration of all
risk factors, treatment, and outcome.
Date amendment: 1 July 2013
The main reason for writing an amendment is that current guidelines on axillary treatment are
changing, both with respect to surgery and with respect to radiation treatment. Not
sufficient data are yet present in literature to define a sound evidence based guideline.
However, recent new data strongly suggest that the guidelines should be adapted. Therefore,
we adapted the guidelines within the framework of this protocol, with as aim to carefully
follow and record the outcome of patients treated with these new guidelines. Whilst writing
this amendment, we also used this opportunity to better define "suspicious nodes" on imaging,
and to add another very relevant endpoint: relapse free survival.
