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The optimal therapeutic approach to THE OLIGOMETASTATIC DISEASE Rita Ceccherini Centro Sociale Oncologico Trieste METASTATIC BREAST CANCER: CURRENT MANAGEMENT.

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Presentation on theme: "The optimal therapeutic approach to THE OLIGOMETASTATIC DISEASE Rita Ceccherini Centro Sociale Oncologico Trieste METASTATIC BREAST CANCER: CURRENT MANAGEMENT."— Presentation transcript:

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2 The optimal therapeutic approach to THE OLIGOMETASTATIC DISEASE Rita Ceccherini Centro Sociale Oncologico Trieste METASTATIC BREAST CANCER: CURRENT MANAGEMENT AND FUTURE PERSPECTIVES Rome, April 23, 2010

3 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

4 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,:

5 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 ?

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

7 MBC Survival improved over time

8 Chia et al:Cancer 2007;110:973-9

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

10 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

11 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

12 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?

13 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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15 MBC chemotherapy trials showing survival benefits TRIALSurvival (months) P valueN of patients (line) First author (year) CAF > CMxF15.2 vs (first)Stewart (1997) Pac > CMFP17.3 vs (first)Bishop (1999) Doc> Mito/VB11.4 vs (second)Nabholtz (1999) APac > FAC23.3 vs (first)Jassem (2001) Cap/Doc > Doc14.5 vs (second )O’Shaughnessy (2002) Chemo + T > Chemo25.1 vs (first)Slamon (2001) Doc +T >Doc31.2 vs (first)Marty (2005) Paclit +Gem > Paclit18.6 vs (first)Albain (2008) Modified from Smith: Annals of Oncology 19 (Supplement 7) 2008

16 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 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

17 Greemberg et al, JCO 1996 Disease patterns and Outcome

18 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

19 Response and Survival

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

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

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

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

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

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

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

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

29 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

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

31 IV NED Breast Cancer Outcomes for the Three Doxorubicin-based Studies, Combined (n=259) 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 SurvivalOverall Survival Hanrah et al : Cancer 104: , 2005

32 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

33 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

34 62 pts minimal disease Local therapy + HDC Nieto et al : J. Clin Oncol 20:707, 2002

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

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

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

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

41 Friedel et al Eur. J. of Cardioth. Surg. 22: , 2002

42 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,:

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

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

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

46 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,:

47 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

48 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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