R. Gaafar - Lung cancer - Guidelines and clinical case presentation (2-3 cases)
Rare Solid Cancers: An Introduction - Slide 7 - A. Berruti - Adrenal cancer
1. Adrenal cancer Alfredo Berruti Dipartimento di Scienze Cliniche e Biologiche Università di Torino Oncologia Medica Azienda Ospedaliera San Luigi Orbassano
2. Malignant ACC Malignant Pheocromocytoma The same gland, two different malignancies
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5. SAN LUIGI SERIES 150 patients NON FUNCTIONING OTHER SECRETIONS VIRILIZATION CUSHING and VIRILIZATION CUSHING COCHIN SERIES, 202 patients NON FUNCTIONING OTHER SECRETIONS VIRILIZATION CUSHING and VIRILIZATION CUSHING CUSHING and OTHER STEROIDS 48% 16% 24% 7% 5% 36% 5% 4% 11% 24% 20%
6. Prognostic role of ACC stage classifications Fassnacht M et al Cancer 2009
9. Clinical pathological parameters associated with malignant behaviour or worse prognosis in 14 studies Weiss score items Volante M et al, J Clin Pathol. 61:787-93, 2008.
10. New prognostic factors The expression of 2 genes: BUB18 and PINK1 predict survival better than tumor stage de Reyniès et al J Clin Oncol 27:1108-1115, 2009
11. Steroidogenic Factor 1 (SF-1) Nuclear transcription factor Expressed almost exclusively in steroid producing organs (adrenal, testes, ovary) and hypothalamus Key regulator of steroidogenesis Leads in vitro and in mice to proliferation of adrenal cells Krylova et al Cell 2005
12. German series (130 pts) French series (38 pts) Sbiera S et al JCEM 95: E161-E171, 2010 Prognostic role of SF-1 in ACC
13. Ann Arbor 2003 Recommendations mainly based on expert opinion Evidence level of available data: II-IV
14. Systemic therapy in adrenocortical cancer patients Therapy Stage I II III IV Surgery + ( R ) + ( R ) + + Systemic Mitotane + + therapy: Chemotherapy +
16. MITOTANE SD: stable disease CR: complete response PR: partial response Studies assessing response with standard criteria NA: not available NR: not retrieved Author; study type Dosage g/die Patients n. Response n., (%) Duration months Henley, 83; r etrospective NR 24 6 PRs (25) 3-24 Venkatesh, 89; r etrospective NR 72 21 PRs (29) NA Luton, 90; retrospective 3-20 37 5 PRs (13) 5-25 Decker, 91; prospective 6 36 2 CRs, 6 PRs (22) 3-82 Pommier, 92; retrospective NA 29 7 PRs (24) NA Haak, 94; retrospective 4-8 55 8 CRs, 7 PRs (27) 2-190 Barzon, 97; retrospective 4-8 11 2 PRs (18) 40-64 Williamson, 99; II line 4-10 16 2 PRs (13) NA Baudin, 01; prospective 6-12 13 1 CR, 3 PRs (33) 10-48
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18. Impact of monitoring o,p‘DDD concentrations Objective tumor response: o,p‘DDD level > 14 g/ml < 14 g/ml Haak et al. 1994 55% 0% Baudin et al. 2001 31% 0% Median interval > 3 months to achieve highest o,p‘DDD trough levels, conc. > 20 g/ml associated with neurological toxicity
19. Stage III-IV ACC survival depends on mitotane plasma levels : a retrospective analysis of 91 patients from 5 european centers ( ENSAT ) Hermsen I et al. JCEM 2011 in press Baudin E IGR 2011
21. At the time of therapeutic initiation plasma mitotane levels and objective response are the strongest predictors of survival Malandrino L et al. ERC 2010 Median survival months yes no Plasma Mitotane > 14 mg/L 19.6 5 Objective response 40.6 9.6
25. FIRM-ACT Recruitment per country Patients are randomized from June 12, 2004 until Sept 17, 2009 Population in million A 8 AUS 28 CAN 33 GER 82 F 64 Italy 60 NL 16 N 5 PL 38 SWE 9 US 311 Total centers (n) 1 1 1 11 9 4 3 2 1 4 2 39 patients (n) 1 3 9 103 71 35 28 5 6 26 17 304
26. ACC : targeted molecular therapies preliminary results Studies / Patients Treatments Method RO-RC Gross D 2006 (4 pts) Imatinig Compassionate WHO 0% Samnotra V 2007 (19pts) Gefinitib Phase II 0% Halusha 2009, 14 pts CP 751-871 Phase I 0% Linsay CR 2009, 10 pts OSI 906 Phase I 10% Quicker M 2008 (10 pts) Erlotinib + Gemcitabine Compassionate RECIST 0% Berruti A (10 pts) Sorafenib + Taxol Phase II RECIST 0% Wortmann S 2010 (10 pts) Bevacizumab Capecitabine + Mitotane Compassionate RECIST 0% Kroiss M 2011 (36 pts) Sunitinib Phase II 0%
32. 131 patients with ACC 102 patients radically resected 4 patients with concomitant other cancers, 3 with heart failure 4 patients underwent other concomitant adjuvant therapies 47 patients treated with adjuvant mitotane (4 centers) 55 patients left untreated (4 centers) 21 patients underwent incomplete, or wedge, or segmental resection 75 german patients left untreated after radical resection
35. Patients 122 patients radically resected for ACC and treated with mitotane in an adjuvant setting since 1996 to 2010. Dept. of Internal Medicine Maxima Medisch Centrum Eindhoven, The Netherlands. Dipartimento di Scienze Cliniche e Biologiche, Medicina Interna 1, Università di Torino, Italy. Department of Nuclear Medicine and Endocrine Oncology, Institut Gustave Roussy, Villejuif, France. Department of Internal Medicine I, Endocrine Unit, University Hospital, University of Würzburg, Germany.
36. 122 patients treated with adjuvant mitotane following radical removal of ACC 55 patients (45 %) attained mitotane concentration ≥ 14 mg/l within 3 months 58 patients ( 47%) attained mitotane concentration ≥ 14 mg/l in > 3 months 10 patients ( 8%) did not ever attain mitotane concentration ≥ 14 mg/l 63 patients (52%) maintained mitotane concentration ≥ 14 mg/l in at least 75% of determinations 59 (48 %) patients did not maintain mitotane concentration ≥ 14 mg/l or did not ever attain them
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39. Alfredo Berruti Martin Fassnacht Eric Baudin Gary Hammer Harm Haak Sophie Leboulleux Britt Skogseid Bruno Allolio Massimo Terzolo JCO , 2010 >
45. Adrenal Cancer team Medical Oncology Paola Sperone Anna Ferrero Paola Perotti Luigi Dogliotti Internal Medicine Fluvia Daffara Arianna Ardito Barbara Zaggia Giuseppe Reimondo Massimo Terzolo Pathology Marco Volante Ida Rapa Mauro Papotti Urology Francesco Porpiglia Department of Clinical and Biological Sciences University of Torino Azienda Ospedaliero Universitaria, San Luigi, Orbassano