Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT02251353 |
| Other study ID # |
IMET |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
June 2014 |
| Est. completion date |
June 2022 |
Study information
| Verified date |
February 2020 |
| Source |
Federation of Breast Diseases Societies |
| Contact |
Lutfi Dogan, MD |
| Phone |
+905057134549 |
| Email |
lutfidogan1[@]yahoo.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
The number of intervention performed for metastatic breast cancer has dramatically increased
over the past 2 decades. Hepatectomy and pulmonary resection for stage IV colorectal cancer
is now considered the standard of care for resectable patients with isolated hepatic and/or
pulmonary disease and acceptable performance status. However, the indications for resection /
intervention of breast cancer origin metastases are not as clearly defined. The aim of this
study to focus on emerging data for the intervention (resection and/or radiofrequency
ablation (RFA), transcatheter arterial chemoembolization (TACE), cyberKnife stereotactic
radiosurgery) of breast cancer metastatic disease to the lung and liver, with a focus on
indications for resection / intervention.
Description:
Purpose Despite breast cancer being the most common cancer in women in the developed world,
only a minority of patients (< 10%) has stage IV disease at diagnosis (1). In addition,
20-30% of patients with early breast cancer will experience distant metastatic relapse (2).
Due to advances in available multimodality therapies and a better understanding of tumor
biology, survival of stage IV patients is constantly improving (3-5).
Clinically, oligometastatic breast cancer is characterized by solitary/few detectable
lesions, usually limited to single organs, in which local therapy with curative intent could
impact survival. This population of 'potentially curable' stage IV disease is estimated to be
1-10% of newly diagnosed patients with metastatic breast cancer (5). A multimodal approach is
endorsed for these selected patients (5,6). The identification of patients with truly
oligometastatic disease is challenging. Most published series refer to an era before modern
imaging (i.e. positron emission tomography-computed tomography), and thus many patients were
probably understaged, potentially leading to underestimation of the global effect of an
aggressive local management.
Patients with oligometastatic disease can be divided into 3 cohorts (7,8): 1) patients who
present with oligometastases; 2) patients with residual oligometastases after systemic
therapy; and 3) those with relapsed oligometastases after curative locoregional therapy.
These different groups have possibly distinct prognoses, and may need differential
approaches.
Several series have reported on lung and liver metastases resection in oligometastatic breast
cancer and most data are from small series of patients collected over many years. The largest
dataset comes from the International Registry of Lung Metastases and presents results of lung
metastasectomy in 467 breast cancer patients (9). Complete resection was possible in 84% of
patients and led to a median survival of 37 months (5-year OS = 38%, 10-year OS = 22%).
Identified prognostic factors for lung resection include disease-free interval and number of
metastases (disease-free interval >36 months and solitary metastases being the most
favorable), ER status, size of metastases, completeness of resection, and use of anatomical
resection (as opposite to wedge resection) (9-19). Obviously, the reported data refer to a
subset of patients who were selected for favorable prognostic factors, and any comparison
with surgically untreated patients is threatened by serious biases.
Pulmonary resection in metastatic breast cancer patients, apart from its potential
therapeutic value, is also an important diagnostic tool, especially in patients with a
suspected first recurrence, allowing for differential diagnosis with second primary lung
cancers and benign lesions (19,20). The proportion of lesions proved not to be breast cancer
metastases in various series ranges from 7% to 66% (9,14,18,21). As the morbidity and
mortality of pulmonary resection has decreased substantially over the last decades, this
potentially beneficial procedure can be discussed in a selected group of patients (9,19,21).
Surgery to remove liver metastases is an accepted treatment modality in patients with
colorectal cancer (22). Its role in breast cancer is, however, much less recognized. Liver is
a common metastatic breast cancer site, but only 5% of patients have isolated liver
involvement. In various series of hepatic resection for breast cancer metastases, the
reported median survival ranged from 14.5 to 63 months and the 5-year survival from 14% to
61%, in general, comparing well with nonsurgically treated patients. Most of the reported
series, however, describe extremely selected patients, constituting 1% or less of metastatic
breast cancer patients treated over the respective periods of time (22-26). As an example, in
the one of the important series, all patients were asymptomatic and identified through
intensive surveillance programs (27). Patients with isolated liver metastasis can potentially
be managed with local treatments (surgery, radiofrequency ablation (RFA), transcatheter
arterial chemoembolization (TACE), cyberKnife stereotactic radiosurgery). In contrast to
liver colorectal metastases, local treatment for breast cancer liver metastasis is not
considered a therapeutic option due to common involvement of additional organs; nevertheless,
in some selected patients, local approaches have been associated with long-term survival
(10,29,30).
Because patients who are potentially eligible for this therapeutic strategy represent only
1%-3% of the total metastatic breast cancer population, a large global collaboration is
needed to confirm its impact on long-term survival or cure and to ensure adequate statistical
power and strength of the results. Enrolled patients must have comparable clinical and
biological characteristics, extent of staging, and frequency of monitoring to avoid selection
biases and stage migration, which can substantially affect the outcome.
The number of intervention performed for metastatic breast cancer has dramatically increased
over the past 2 decades. Hepatectomy and pulmonary resection for stage IV colorectal cancer
is now considered the standard of care for resectable patients with isolated hepatic and/or
pulmonary disease and acceptable performance status. However, the indications for resection /
intervention of breast cancer origin metastases are not as clearly defined. The aim of this
study to focus on emerging data for the intervention (resection and/or radiofrequency
ablation (RFA), transcatheter arterial chemoembolization (TACE), cyberKnife stereotactic
radiosurgery) of breast cancer metastatic disease to the lung and liver, with a focus on
indications for resection / intervention.
Patient acquisition and data collection All patient should be female. All following
demographic, clinical and tumour specific data will be collected: patient age, performance
status according to the WHO classification at the time of first presentation to the hospital,
stage, type and receptor status (ER, PR, HER-2) of the primary tumour, tumor load in the lung
and/or liver (uni-or bilateral affection, number of metastases, diameter of the largest
tumour size), chronology of the metastases (metachronous or synchronous), presence of further
metastatic (synchronous metastases) or recurrent (metachronous) extrahepatic tumour growth
and lymph node involvement in the mediastinal region or hepatoduodenal ligament. In addition,
treatment-related and follow-up data will be documented: Intervention method (surgical
resection, cryosurgery, laser-induced thermotherapy, radio-frequency ablation, ethanol
injection, cyber-knife), median follow-up, incidence of tumour recurrence, time to
recurrence, overall survival, and the administration of chemotherapy. Survival will be
calculated from the date of diagnosis of the lung and/or liver metastases.
Definitions Lung and/or liver metastases will be defined as metachronous if the interval
between resection of the primary tumour and first diagnosis of metastases is longer than 3
months. General physical condition of study patients will be measured by the performance
status according to the WHO classification.
Prior and during the treatment, all patients will be undergone evaluation with complete
medical history, physical examination, baseline blood tests, and imaging evaluations
(positron emission tomography (PET-CT) and/or radiography, bone scintigraphy, computed
tomography scan, magnetic resonance imaging, ultrasonography). Effects of the treatment will
be monitoring by imaging analyses at every 3 months for lesions detected at diagnosis of lung
and/or hepatic metastasis or every 6 months without detectable lesions before the treatment.
R0 resection is a complete resection with no microscopic residual tumor, while R1 resection
means a complete resection with no grossly visual tumor as defined by surgeon, but
microscopic cancer may be left behind. R2 resection indicates a partial resection with
grossly visible tumor left behind.
Effects of the treatment were assessed by analyses of maximum response, according to either
the criteria of the World Health Organization (WHO) (30) or the Response Evaluation Criteria
in Solid Tumors (RECIST) version 1.0 (31) since its announcement in 2004. Responses in bone
metastases were evaluated using the methods reported by MD Anderson Cancer Center (32,33),
with CR as clear evidence of complete bone recalcification with attainment of near-normal
bone architecture or normalization of scan, and partial response as radio- logical evidence
of sclerosis in lytic lesions or marked improvement of bone scan. In recent years, MRI was
performed when available, and the imaging information was taken into account in evaluation of
bone metastases. Responses in pleural fluids were determined as: CR for radiological
demonstration of complete disappearance of pleural fluid, and PR for 50% or more decrease.
For study inclusion, pathological diagnosis of the primary lesions had to be obtained,
whereas tissue or cellular pathology of the metastatic lesions was preferred but not
mandatory. In patients who performed surgical resection, a complete histopathological
response will be defined as the absence of vital tumour cells. Detection of tumour necrosis
or scar formation within the tumour tissue will be regarded as a partial pathohistological
response.
Ethics committee approval in Istanbul University Istanbul Medical Faculty can be obtained to
participate for this study.
Statistical analysis The characteristics of the patients with assessable data will be
compared with X2 test or Wilcoxon rank-sum tests. Overall survival (OS) will be defined as
duration from diagnosis of the metastasis to last visit or death. Progression free interval
(PFI) will be defined as duration from diagnosis of the metastasis to the point when disease
progression will be detected. Complete response (CR) will be achieved by a systemic therapy
or no evidence of clinical disease (NED) after a local therapy considered relapse-free, and
the duration between induction of relapse free status and the point of relapse detection will
be defined as the relapse free interval (RFI); survival time after induction of relapse-free
status without relapse will be defined as relapse free survival (RFS). Unrelated death other
than from breast cancer will be considered as censored in evaluation of PFI and RFI. Survival
curves will be calculated according to the Kaplan-Meier method. The log-rank test will be
used to evaluate differences in survival between groups with intervention and
no-intervention. A multivariate analysis will be performed by Cox regression and the
following variables will be included: age, DFI, performance status (PS), liver metastasis,
pulmonary metastasis, presence of other metastasis, hormone receptor status, HER2 status,
Ki-67 status, intrinsic subtype, administration of local therapy, and chemotherapy regimens.
Statistical significance will be defined as a p value <0.05. All p values will be calculated
for two-sided analyses. For observed survival, all deaths will be considered as events
including patients who died from secondary causes without recurrence. Statistical analyses
will be performed using SPSS 22.0 (SPSS, Chicago, IL) software.
