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The optimal therapeutic approach to THE oligometastatic disease

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Presentation on theme: "The optimal therapeutic approach to THE oligometastatic disease"— Presentation transcript:

1 The optimal therapeutic approach to THE oligometastatic disease
Metastatic Breast Cancer: current management and future perspectives Rome, April 23, 2010 The optimal therapeutic approach to THE oligometastatic disease Rita Ceccherini Centro Sociale Oncologico Trieste

2 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

3 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,:

4 Can MBC be cured ? Prolungation of survival Symptoms relief
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 ?

5 Biases Definition of “cure”
Influence of the new technologies to detect minimal residual disease Most MBC trials have relatively short follow-up

6 MBC Survival improved over time

7 MBC Survival improved over time
Chia et al:Cancer 2007;110:973-9

8 Survival in Metastatic Breast Cancer. A Population Based Analysis
MORE TOOLS , MORE LIFE Median days survival P<. 001 P=.01 Taxol & Vinorelbine Taxotere & AI Xeloda & Herceptin Si Chia et al:Cancer 2007;110:973-9

9 PATIENT-RELATED FACTORS
Factors to consider in risk assessment and treatment decision making for MBC DESEASE-RELATED FACTORS PATIENT-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’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

10 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

11 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?

12 Survey of TREATMENT RESULTS
ROLE OF SYSTEMIC TREATMENT ROLE OF LOCAL TREATMENT Conventional Chemotherapy High-dose Chemotherapy Adjuvant systemic after local treatment Surgery for Primary Tumor in the presence of limited metastatic disease Surgery for Lung and liver metastases

13 Conventional Chemotherapy

14 MBC chemotherapy trials showing survival benefits
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 11.5 511(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

15 Between 1973 to 1982 1581 patients 263 RC (16.6%)
Long-Term Follow-Up of Patients With Complete Remission Following Combination Chemotherapy for Metastatic Breast Cancer Between 1973 to 1982 1581 patients 263 RC (16.6%) 49 NED after 5 years (3.1%) 26 NED after 15 years (1.5%) 4 Died in CR after months Greenberg et al, J Clin Oncol 1996

16 Disease patterns and Outcome
Tumor burdens (as measured by the Swenerton semi-quantitative index of tumor extent"), Greemberg et al, JCO 1996 16

17 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

18 Response and Survival

19 Response to chemotherapy is a mayor parameter-influencing long-term survival in metastatic breast cancer patients 1430 patients from 1977 to 1992 8 trials antracycline-based first-line chemotherapy Median follow up 155 months Pierga et al: Annals of Oncology 12: , 2001

20 MBC first –line doxorubicin-containing chemotherapy: Effect of adjuvant chemotherapy on outcome
Pierga et al: Cancer 2001; 91:

21 MBR first –line doxorubicin-containing chemotherapy: Effect of adjuvant chemotherapy on outcome
Overall survival Survival according with CT type Pierga et al: Cancer 2001; 91:

22 6 randomized controlled trials NO HDC OUTSIDE OF CLINICAL TRIALS
Is there a role for HDC? 6 randomized controlled trials HDC 438 patients CC 412 patients OS: no difference More toxicity NO HDC OUTSIDE OF CLINICAL TRIALS Farquhar et al: Cochrane Database Syst Rev 2005; (3) CD003142

23 “Adjuvant “ Systemic Therapy after local treatment

24 Stage IV NED Primary Breast Cancer Surgery +/or Radiotherapy +/-
Adjuvant Systemic Therapy Solitary Metastasis Surgical Resection +/- Radiotherapy Stage IV NED (No Evident Disease)

25 N.S P=0.053 DFS by treatment Overall Survival
Waeber et al: Annals of Oncology 14:1215, 2003

26 Adjuvant Chemotherapy in Stage IV NED
Rivera et al: The Breast J: 8; 2-9, 2002

27 Adjuvant Therapy in Stage IV NED
Rivera et al: The Breast J: 8; 2-9, 2002

28 Disease-free survival of patients with stage IV-NED breast cancer according to study group
Rivera et al: The Breast J: 8; 2-9, 2002

29 Overall survival of patients with stage IV-NED breast cancer according to study group
Rivera et al: The Breast J: 8; 2-9, 2002

30 Disease-free Survival Overall Survival
IV NED Breast Cancer Outcomes for the Three Doxorubicin-based Studies, Combined (n=259) Disease-free Survival Overall Survival 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% Hanrah et al : Cancer 104: , 2005

31 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: , 2005

32 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: , 2005

33 62 pts minimal disease Local therapy + HDC Nieto et al : J. Clin Oncol 20:707, 2002

34 P= P= .03 P=.0008 Nieto et al : J. Clin Oncol 20:707, 2002

35 for primary tumor in the presence of metastatic disease
Surgery for primary tumor in the presence of metastatic disease

36 MBC : Surgery for primary tumor
3.5% -7% MBC at diagnosis 7.000 new patients /year 50% T1-T3 primary tumor Surgery?

37 MBC : Surgery for the intact primary
Pagani et al: J Nat Cancer Inst 2010;102,:

38 Surgery for lung and liver metastases

39 Surgical resection of lung metastasis
Pagani et al: J Nat Cancer Inst 2010;102,:

40 Friedel et al Eur. J. of Cardioth. Surg. 22: 335-344, 2002

41 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,:

42 Surgical resection of isolated liver metastases
Pagani et al: J Nat Cancer Inst 2010;102,:

43 Hepatic resection in MBC: results and prognostic factors
Pocard et al Eur J Oncol 26:155, 2000

44 Hepatic resection in MBC: results and prognostic factors
Pocard et al Eur J Oncol 26:155, 2000

45 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,:

46 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

47 clinical consequences
CONCLUSIONS Oligometastatic 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 ?


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