Riunione del Gruppo di Studio Chirurgico Oncologico. Tumori dell adolescente: L esperienza del Gruppo TREP

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1 Riunione del Gruppo di Studio Chirurgico Oncologico Tumori dell adolescente: L esperienza del Gruppo TREP

2 The TREP project: defining Very Rare Pediatric Tumors an arbitrary and pragmatic definition epidemiologic criteria: any solid malignancy characterized by an annual incidence <2 cases/million/children strategic criteria: and not considered in other clinical trials nasopharyngeal carcinoma adrenocortical tumors pleuro-pulmonary blastoma (and other lung tumors) carcinoid tumors cutaneous melanoma renal cell carcinoma pancreatoblastoma (and other pancreatic exocrine tumors) gonadal non-germ-cell tumors (ovary/testis) pheochromocytoma and paraganglioma thyroid carcinoma salivary gland tumors breast carcinoma carcinoma of the gastrointestinal tract carcinoma of the thymus other rare malignant and borderline tumors

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4 Very rare cancers in children - The EXPeRT initiative: A Report from the European Cooperative Study Group on Pediatric Rare Tumors Gianni Bisogno* 1, Andrea Ferrari* 2, Ewa Bien 3, Ines B. Brecht 4, Bernadette Brennan 5, Giovanni, Cecchetto 6, Jan Godzinski 7, Daniel Orbach 8, Yves Reguerre 9, Teresa Stachowicz-Stencel 10, Dominik T. Schneider* 11 Therefore, a pragmatic definition of a potential EXPeRT cohort of patients has to be defined that took the specific national aspects into account: any solid malignancy or borderline tumor characterised by an annual incidence < 2/million and/or not already considered in other clinical trials. This definition considers both the epidemiological and clinical criteria. It takes the need of children to benefit from a dedicated network into focus thus defining EXPeRT as a cooperative group that primarily aims to improve the clinical care for children with VRTs.

5 Da una prospettiva diversa: I tumori rari nei bambini sono spesso tumori frequenti

6 adults N rate* Renal cell carcinoma 98, Hepatocarcinoma 41, Adrenocortical carcinomas 1, Thyroid carcinomas 80, Nasopharyngeal carcinomas 7, Malignant melanomas 187, Carcinomas of salivary glands 12, Carcinomas of colon/rectum 584, Carcinomas of lung 618, Carcinomas of thymus 2, Carcinomas of breast 752, Carcinomas of cervix uteri 59, Carcinomas of bladder 135, Carcinomas of other sites 1,309, Gastrointestinal stromal tumor 3, Mesothelioma 10, Total 4,121, N rate* N rate* , , < < < < < ,032 6,457 number of cases registered in the Survival Epidemiology and End Result (SEER) database ( ) and incidence rates (per 100,000 population*).

7 Progetto TREP: il reclutamento 0-14 yrs yrs Cancer Types O E O/E (95%CI) O E O/E (95%CI) nasopharyngeal carcinoma ( ) ( ) adrenocortical tumors ( ) ( ) pleuro-pulmonary blastoma ( ) carcinoids of appendix ( ) ( ) cutaneous melanoma ( ) ( ) renal carcinoma ( ) ( ) pancreatoblastoma ( ) ( ) gonadal non-germ-cell tumors ( ) ( ) pheochromocytoma ( ) thyroid carcinoma ( ) ( ) salivary gland tumors ( ) ( ) breast carcinoma carcinoma of the GI tract ( ) ( ) carcinoma of the thymus E expected O observed Bambini Adolescenti

8 TREP: bambini e adolescenti No. of pts Carcinoid tumors Thyroid carcinoma Cutaneous tumors Nasopharyngeal carcinoma Non germ cell gonadal tumors Renal carcinoma Pancreatic tumors Adrenocortical carcinoma Pheochromocytoma Pleuropulmonary blastoma Others Salivar glands tumors Thymic tumors Gastrointestinal tumors Breast tumors

9 Carcinoma della Tiroide Clinical characteristics: Carcinoma Papillare More aggressive in children: 50% pluricentric at onset 70% extended beyond the thyroid capsule 70% nodal metasasis 20% distant metastasis (lung) Biology: RET/PCR3 translocation vs BRAF mutation in adult tumors Therapy: TSH suppression therapy (l-thyroxin) is extremely effective in controlling tumor growth Outcome: Survival 100% in children

10 Papillary carcinoma in children A different therapeutic approach? AGGRESSIVE (as in adults) improve progression-free survival by detecting and treating all tumor cells, and preventing any dedifferentiation of occult neoplastic micro-foci eradication of all clinical and subclinical neoplastic foci (at T, N and M) total thyroidectomy (regardless of the tumor extent) prophylactic lymphadenectomy RAI scintigraphic scan to look for any subclinical metastases treatment with 131 I ablation, where necessary serum thyroglobulin level is a very sensitive marker of post-treatment relapse hypoparathyroidism (36%) recurrent laryngeal nerve paralysis and spinal accessory nerve paralysis (28%) Risk of iatrogenic effects of metabolic RT aims strategy thyroid resection Lymphadenectomy staging post-operative treatment follow-up risk of permanent morbidity CONSERVATIVE for selected pediatric patients (tumors limited to 1 lobe ± clinical evidence of monolateral N) contain treatment morbidity, without compromising survival (the risk of tumor dedifferentiation from microscopic disease seems to be merely theoretical in children) remove only grossly detectable disease, without searching for microscopic disease after surgery hemithyroidectomy removal of the clinically affected thyroid lobe selective dissection (only the clinically involved node levels) No RAI scintigraphic scan (macrostaging instead of microstaging) TSH suppression therapy to control subclinical disease presence of thyroid tissue would prevent the effective use of thyroglobulin assay as a marker of tumor relapse very low

11 Carcinoma della Tiroide Bambini vs adolescenti vs adulti

12 Carcinoide dell appendice 102 pazienti Età Mediana 12.3 anni 49% dei pazienti > 12 anni età e dimensioni tumore: nessuna correlazione significativa (però 4 tumori > 2 cm in pazienti > 13 anni Risultato buono (sopravvivenza 100%) con trattamento conservativo

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14 Carcinoma Nasofaringeo Bambini vs adolescenti vs adulti Buoni risultati riducendo Il trattamento

15 Carcinoma Colon Retto

16 Distinctive features in children: advanced disease at onset (aggressive tumors, delay in diagnosis) unfavourable histotypes (poorly differentiated, mucinous adenoca) Familiarity (HNPCC and FAP) 14% children, 55% young adults, 13% adults

17 La rarità del CCR e l esperienza limitata potrebbero contribuire al risultato negativo visto nei bambini con CCR? L esperienza del chirurgo e il suo livello di training sembrano avere un valore prognostico nel CRC dell adulto A.J. Simons et al. Dis Colon Rectum 1997; 40: J Goligher. Dis Colon Rectum 1997; 40: General Hospital Approved Hospital SSP General Surgeons colorectal surgeons LR all pts LR Dukes C

18 Carcinoma Colon Retto Bambini vs adolescenti vs adulti Eccezionale Prognosi peggiore

19 Carcinoma Renale 41 bambini (18/23 M/F) Età mesi (mediana 10 anni)

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21 8/9 RLND vivi NED 1/4 LFN para-aortici vivo NED Conclusioni: N1 fattore prognostico negativo I risultati sembrano migliori rispetto agli adulti

22 Metastatic Renal Cell Carcinoma in Children and Adolescents: A 30 Years Unsuccessful Story Paolo Indolfi,MD 1*, Filippo Spreafico, MD, 2 Paola Collini, MD, 2 Giovanni Cecchetto, MD, 3 Fiorina Casale, MD, 1 Monica Terenziani, MD, 2 Amalia Schiavetti, MD, 4 Paolo Pierani, MD, 5 Luigi Piva, MD, 2 Daniela Cuzzubbo, MD, 6 Maria Debora De Pasquale, MD, 7 Elvira Pota, MD, 1 Alessandro Inserra, MD, 7 and Gianni Bisogno, MD, 3 14 patients: 6 chemotherapy 9 immunotherapy 2 adjuvant antiangiogenic therapy. 11 patients (78.5%) never achieved complete remission and died from progressive disease 3 patients, two of whom received adjuvant antiangiogenic therapy, relapsed to lung and died

23 Carcinoma Renale bambini = adolescenti = adulti (?)

24 Tumori pancreatici (in una diapo) Pancreatoblastoma: anni bambini Carcinoma 3 6,7,7 anni Tumore neuroendocrino 1 15 Tumore pseudopapillare anni adolescenti

25 GIST (in una diapo) Adult GIST currently recognized as the most frequent mesenchymal tumors incidence around 1-1.5/100,000/year Pediatric GIST SEER : 12 cases (6 < 14 years) incidence 0.02/1,000,000/year

26 Progetto TREP: il reclutamento ORL Chirurghi Dermatologi 0-14 yrs yrs Cancer Types O E O/E (95%CI) O E O/E (95%CI) nasopharyngeal carcinoma ( ) ( ) adrenocortical tumors ( ) ( ) pleuro-pulmonary blastoma ( ) carcinoids of appendix ( ) ( ) cutaneous melanoma ( ) ( ) renal carcinoma ( ) ( ) pancreatoblastoma ( ) ( ) gonadal non-germ-cell tumors ( ) ( ) pheochromocytoma ( ) thyroid carcinoma ( ) ( ) salivary gland tumors ( ) ( ) breast carcinoma carcinoma of the GI tract ( ) ( ) carcinoma of the thymus Urologi Ginecologi Endocrinologi Chirurghi Maxillo-facciali E expected O observed Bambini Adolescenti

27 TREP Tumori tipici del bambini Tumori tipici dell adulto che insorgono nel bambino

28 Tumori dell adulto nei bambini Caratteristiche cliniche e biologiche diverse Stessa terapia? Approccio al paziente e alla famiglia C. Tiroide, GIST, Carcinoma, retto, fibrosarcoma,.. Adulti e bambini possono presentare differenze nel metabolismo dei farmaci e nella tossicità. L approccio chirurgico e radioterapico è diverso Ambiente pediatrico vs adulto

29 Adolescenti con tumori rari Tumori non così rari Caratteristiche cliniche e biologiche simili a quelle dei bambini o degli adulti? Tumori più noti ad altri specialisti che all oncologo pediatra Dove vanno curati?

30 Perché l oncologia pediatrica dovrebbe interessarsi ai tumori rari negli adolescenti? Abitudine a lavorare con tumori rari Approccio specifico all adolescente Attenzione agli effetti collaterali a lungo termine Possibilità di collaborazione Possibilità di ricerca

31 Progetto TREP: la possibile/necessaria collaborazione ORL Chirurghi Dermatologi 0-14 yrs yrs Cancer Types O E O/E (95%CI) O E O/E (95%CI) nasopharyngeal carcinoma ( ) ( ) adrenocortical tumors ( ) ( ) pleuro-pulmonary blastoma ( ) carcinoids of appendix ( ) ( ) cutaneous melanoma ( ) ( ) renal carcinoma ( ) ( ) pancreatoblastoma ( ) ( ) gonadal non-germ-cell tumors ( ) ( ) pheochromocytoma ( ) thyroid carcinoma ( ) ( ) salivary gland tumors ( ) ( ) breast carcinoma carcinoma of the GI tract ( ) ( ) carcinoma of the thymus Urologi Ginecologi Endocrinologi Chirurghi Maxillo-facciali E expected O observed Bambini Adolescenti

32 Il Progetto TREP: i possibili sviluppi from: to: EXPeRT European Cooperative Study for Pediatric Rare Tumors

33 The TREP project: RINGRAZIAMENTI the TREPpers Gianni Bisogno Giovanni Cecchetto Andrea Ferrari E.Mancini G.L. De Salvo TREP project co-coordinators data manager responsible Data Center ESPERTI TREP: P. Indolfi, M. Massimino, A. Inserra, C. Spinelli, M. Casanova, P. Dall Igna, G. Bernini, G. Magro, R. Alaggio, R. Boldrini, P. Collini, C. Gambini Il progetto TREP è stato supportato da: