the optimal therapeutic approach to the oligometastatic disease rita ceccherini centro sociale...
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The optimal therapeutic approach toTHE OLIGOMETASTATIC DISEASE
Rita CeccheriniCentro Sociale Oncologico Trieste
METASTATIC BREAST CANCER: CURRENT MANAGEMENT AND FUTURE PERSPECTIVES
Rome, April 23, 2010
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OLIGOMETASTASIS • …..“In some tumors the anatomy and physiology may
limit or concentrate these metastases to a single or a limited number of organs”……
……“An attractive consequence of
a “clinically significant “
OLIGOMETASTATIC STATE
is that some patients should be amenable to a curative therapeutic strategy……..
Hellman S, Weichselbaum RR: J Clin Oncol 1995;13:8-10, modified
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Potentially curable Stage IV (1-10%)ESO-MBC Task-Force Consensus
• “A small but very important subset of MBC patients, for example those with a solitary metastatic lesion, can achieve complete remission and a long survival.
• A more aggressive and multidisciplinary approach schould be considered for these selected patients.
•
• A clinical trial addressing this specific situation is needed
Pagani et al: J Nat Cancer Inst 2010;102,:456-463
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GOALS OF THERAPY IN MBC
• Prolungation of survival • Symptoms relief• Maintenance of a good quality of life• Delay of disease progression
Can MBC be cured ?
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Biases• Definition of “cure”
• Influence of the new technologies to detect minimal residual disease
• Most MBC trials have relatively short follow-up
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MBC Survival improved over time
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MBC Survival improved over time
Chia et al:Cancer 2007;110:973-9
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Survival in Metastatic Breast Cancer. A Population Based Analysis
438 450
564667
0
100
200
300
400
500
600
700
1991-2 1994-5 1997-8 1999-01
Taxo
l & V
inor
elbi
neTa
xote
re &
AI
Xelo
da &
Her
cept
in
MORE TOOLS , MORE LIFE
Chia et al:Cancer 2007;110:973-9
Median days survival
P=.01P<. 001
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Factors to consider in risk assessment and treatment decision making for MBC
DESEASE-RELATED FACTORS
• Disease-free interval
• Tumor burden (number and sites of metastases)
• Prior therapies and response
• Biological factors (Hormonal receptors, HER2)
• Need for rapid disease/symptom control
PATIENT-RELATED FACTORS
• Patient’s preferences
• Biological age
• Menopausal status
• Co-morbididities and performarce status
• Socio-economic and psychological
Available therapies in the patient’s country
Cardoso &Castiglione: Annals of Oncology 20 (Suppl 4), 2009
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Characteristics of the Long-Term Disease-Free Survivors
• Limited metastatic disease (one organ site involved)
• Young age• Excellent performance status• No adjuvant chemotherapy• Normal organ function• Absence of significant co-morbidity
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Oligometastatic state in breast cancer: hypothesis or reality?
• Are there patients whose survival improvement could translate into cure?
• How many are they?
• How can we select patients who are likely to benefit curative treatment?
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SURVEY OF TREATMENT RESULTS
ROLE OF SYSTEMIC TREATMENT
• Conventional Chemotherapy
• High-dose Chemotherapy
• Adjuvant systemic after local treatment
ROLE OF LOCAL TREATMENT
• Surgery for Primary Tumor in the presence of limited metastatic disease
• Surgery for Lung and liver metastases
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MBC chemotherapy trials showing survival benefits
TRIAL Survival (months)
P value N of patients (line)
First author (year)
CAF > CMxF 15.2 vs 10.9 0.003 249 (first) Stewart (1997)
Pac > CMFP 17.3 vs 13.9 0.025 209 (first) Bishop (1999)
Doc> Mito/VB 11.4 vs 8.7 0.0097 392 (second) Nabholtz (1999)
APac > FAC 23.3 vs 18.3 0.013 267 (first) Jassem (2001)
Cap/Doc > Doc 14.5 vs 11.5 0.013 511(second ) O’Shaughnessy (2002)
Chemo + T > Chemo 25.1 vs 20.3 0.046 469 (first) Slamon (2001)
Doc +T >Doc 31.2 vs 22.7 0.0325 186 (first) Marty (2005)
Paclit +Gem > Paclit 18.6 vs 15.8 0.02 529 (first) Albain (2008)
Modified from Smith: Annals of Oncology 19 (Supplement 7) 2008
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Long-Term Follow-Up of Patients With Complete Remission Following Combination Chemotherapy for Metastatic Breast Cancer
Greenberg et al, J Clin Oncol 1996
Between 1973 to 19821581 patients 263 RC (16.6%)
•49 NED after 5 years (3.1%)•26 NED after 15 years (1.5%)•4 Died in CR after 118-234 months
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Greemberg et al, JCO 1996
Disease patterns and Outcome
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Results and Long Term Follow-up for 1581 patients with MBC Treated with
Standard dose Doxo-Containing Regimens
Rahman et al: Cancer 1999;85:104-11
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Response and Survival
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Response to chemotherapy is a mayor parameter-influencing long-term survival in metastatic breast cancer patients
Pierga et al: Annals of Oncology 12:231-237, 2001
•1430 patients from 1977 to 1992
•8 trials antracycline-based first-line chemotherapy
•Median follow up 155 months
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MBC first –line doxorubicin-containing chemotherapy: Effect of adjuvant chemotherapy on outcome
Pierga et al: Cancer 2001; 91: 1079-1089
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MBR first –line doxorubicin-containing chemotherapy: Effect of adjuvant chemotherapy on outcome
Pierga et al: Cancer 2001; 91: 1079-1089
Overall survival Survival according with CT type
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Is there a role for HDC?
Farquhar et al: Cochrane Database Syst Rev 2005; (3) CD003142
6 randomized controlled trials
HDC438 patients
CC412 patients
OS: no difference More toxicity
NO HDC OUTSIDE OF CLINICAL TRIALS
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Stage IV NED
Primary Breast Cancer
Surgery +/or Radiotherapy +/- Adjuvant Systemic Therapy
Solitary Metastasis
Surgical Resection +/- Radiotherapy
Stage IV NED (No Evident Disease)
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DFS by treatment Overall Survival
Waeber et al: Annals of Oncology 14:1215, 2003
N.SP=0.053
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Adjuvant Chemotherapy in Stage IV NED
Rivera et al: The Breast J: 8; 2-9, 2002
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Adjuvant Therapy in Stage IV NED
Rivera et al: The Breast J: 8; 2-9, 2002
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Disease-free survival of patients with stage IV-NED breast cancer according to study group
Months
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0 24 48 72 96 120 144 168 192 216 240
Study 3 (45 Pts)
Study 2 (80 Pts)
Study 1 (134 Pts)
Control (62 Pts)
P < 0.001
Rivera et al: The Breast J: 8; 2-9, 2002
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Overall survival of patients with stage IV-NED breast cancer according to study group
Rivera et al: The Breast J: 8; 2-9, 2002
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IV NED Breast CancerOutcomes for the Three Doxorubicin-based Studies, Combined (n=259)
0.0
0.2
0.4
0.6
0.8
1.0
0 100 200 300 400
Months from Treatment
Dis
ease
-Fre
e S
urvi
val P
roba
bilit
y
Median DFS: 42 mos
3-yr DFS: 57%
5-yr DFS: 41%
10-yr DFS: 34%
20-yr DFS: 26%
Median 0S: 87 mos
3-yr DFS: 75%
5-yr DFS: 56%
10-yr DFS: 42%
20-yr DFS: 26%
Disease-free Survival Overall Survival
Hanrah et al : Cancer 104: 1158-1171, 2005
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Docetaxel-based trial duration and probability of overall survival (26 patients prior adjuvant antracycline based chemotherapy)
Median follow-up 44 months
3-yr DFS: 58%
Hanrah et al : Cancer 104: 1158-1171, 2005
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Combined-Modality Treatment for Isolated Recurrences of Breast Carcinoma Update on 30 Years of Experience M. D. Anderson Cancer Center
Assessment of Prognostic Factors
Hanrah et al : Cancer 104: 1158-1171, 2005
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• 62 pts minimal disease
• Local therapy + HDC
Nieto et al : J. Clin Oncol 20:707, 2002
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P= .000.4P= .03
P=.0008
Nieto et al : J. Clin Oncol 20:707, 2002
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MBC : Surgery for primary tumor
• 3.5% -7% MBC at diagnosis
• 7.000 new patients /year
• 50% T1-T3 primary tumor
Surgery?
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MBC : Surgery for the intact primary
Pagani et al: J Nat Cancer Inst 2010;102,:456-463
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Surgical resection of lung metastasis
Pagani et al: J Nat Cancer Inst 2010;102,:456-463
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Friedel et al Eur. J. of Cardioth. Surg. 22: 335-344, 2002
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Lung resection: important diagnostic tool
From 7% to 66%
second primary lung cancer
and benign lesion
Pagani et al: J Nat Cancer Inst 2010;102,:456-463
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Surgical resection of isolated liver metastases
Pagani et al: J Nat Cancer Inst 2010;102,:456-463
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Hepatic resection in MBC: results and prognostic factors
Pocard et al Eur J Oncol 26:155, 2000
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Hepatic resection in MBC: results and prognostic factors
Pocard et al Eur J Oncol 26:155, 2000
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ESO-MBC Task-Force Consensus
• “A small but very important subset of MBC patients, for example those with a solitary metastatic lesion, can achieve complete remission and a long survival.
• A more aggressive and multidisciplinary approach schould be considered for these selected patients.
•
• A clinical trial addressing this specific situation is needed
Pagani et al: J Nat Cancer Inst 2010;102,:456-463
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Characteristics of the Long-Term Disease-Free Survivors
• Limited metastatic disease (one organ site involved)
• Young age• Excellent performance status• No adjuvant chemotherapy• Normal organ function• Absence of significant co-morbidity
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CONCLUSIONSOligometastatic state in breast cancer hypothesis or reality?
CLINICAL CONSEQUENCES
• selected subset of oligometastatic MBC patients should be approached with curative intent
• the current minimalistic postoperative follow-up schould be revised to allow early diagnosis of low-burden disease relapse ?