Mediastinal tumours. the oncological view. D. Betticher, Medical Oncology, Cantonal Hospital Fribourg, Switzerland
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1 Mediastinal tumours the oncological view D. Betticher, Medical Oncology, Cantonal Hospital Fribourg, Switzerland
2 Mediastinal tumours Clavicula Antero-superior Intermediary Posterior D4 Antero-superior Thymoma, Teratoma, teratocarcinoma Thyroidea Mesothelioma Sarcoma Lipom(-sarcoma) Intermediary Lymphoma Lymph node metastases Cardiac / pericardiac tumour Posterior Neurofibroma/-blastoma/- sarcoma Pheochromocytoma Chordoma Esophageal cancer Paraganglioma, PNET
3 Case report 1 Men, 54 y old, Non-smoker No symptoms so far Fever: chest X-ray: med. tumour Normal blood values
4 Case report 1 BM infiltration Infiltration of the colon Mucosa CT: CHOP + Mabthera depending on results autologous BMT
5 Case report 2 Woman, - 60 years old - no symptoms - feels cervical lymphadenopathy Chest X Ray
6 Anterior med. tumour CT scan Lab values: - normal blood values - normal renal and liver function - LDH normal α-foetoproteine/β HCG normal
7 T-cell lymphoblastic lymphoma Histology: ReferencecentreSt. Gallen and CHUV: T-cell LL Patient refused CT After 6 months slight decrease of tumour mass
8 Case report 3 Men, 80 y old Some cough Comorbidities: cardiac and renal failure hypothyroidea Chest X ray: med. tumour
9 6/2006
10 6/ /2007
11 ?? Mediastinal fibrositis: Male:female = 3:1 pathogenesis Two histologic types: Chronic fibrosis, avascular, acellular Fibrosis with inflammatory cells (lymphocytes, plasmocytes, eosinophils, russel bodies, fibroblasts) Suggested = auto-immune disease: IgG4 autoimmune reaction by plasma cells (pancreatitis) Secondary to a local autoallergic reaction: atherosclerotic plaques Tanabe T. et al., Int. Med., 2006, 45, 1243 Szarf G. et al., Radiology 2005, 235, 829 Oguz KK et al., Eur. Radiol, 2002, 12, 1134
12 Mediastinal fibrositis Fibrosis involving multiple organ systems Perivascular (aortic disease) Kidneys Glands (pancreatic, lacrymal) Stomach Choriod plexus Small bowel and mesocolon Inciting/risk factors: Malignancies Radiotherapy Surgery, hemorrhage Retroperitoneal infection Autoimmune disease Therapy: steroids if necessary Szarf G. et al., Radiology 2005, 235, 829 Oguz KK et al., Eur. Radiol, 2002, 12, 1134
13 Case report 4 Female, 28 years old Cough, Dyspnea, Fatigue, fever Chest X Ray
14 Case report 4
15 Diagnosis: PNET Tumour Intensive chemotherapy Resection of the remaining tumour Radiotherapy Further chemotherapy cycles
16 PNET: the primitive neuroectodermal tumour Belongs to the Ewing s sarcoma family of tumours (EFT) Bone or soft tissue Ewing sarcoma PNET (Askin tumour, small-cell tumor of the thoracopulmonary region) Adult neuroblastoma Paravertebral small-cell tumor Second most common sarcoma in children and adolescents Grier HE: Pediatr. Clin. North Am. 1997, 44, 991
17 PNET: Histology Monotonous sheets of small round cells with hyperchormatic nuclei and scant cytoplasm that is clear because of abundant glycogen De Alva E., et al., J. Clin. Oncol. 2000, 18, 204
18 PNET: Cytogenetics Type of sarcoma / translocations Genes Type of fusion gene Ewing sarcoma (t(11;22)(q24;q12); t(21;22)(q22;q12); t(7;22)(p22;q12); t(17;22)(q21;q12); t(2;22)(q33;q12) EWSR1 Transcritpion factor Clear cell sarcoma/pnet /PNET: t(12;22)(q13;q12) Small round cell tumour of the abdomen: t(12;22)(p13;q12) EWSR1 EWSR1 Transcription factor Transcription factor Chondrosarcoma: t(9;22)(q22-31;q12) EWSR1 Transcription factor Liposarcoma: t(12;22)(q13;q12) EWSR1 Transcription factor EFT: all cases express one of several different reciprocal translocations, all involving the breakpoint of the gene locus EWS on chr. 22 De Alva E. et al., J. Clin. Oncol. 2000, 18, 204
19 PNET: Therapy Referral to centres that have a multidisciplinary approach Usually, treatment starts with chemotherapy The primary tumour can be treated by surgery and/or radiotherapy Following local treatment, chemotherapy is usually continued for several months (total duration of treatment = 12 months) Relapse: role of high dose and autologous BMT is unclear
20 PNET tumours 17 courses for 49 weeks* Doxorubicine, Cyclosphosphamide Dactinomycine, Vincristine = standard therapy 530 patients 17 courses for 49 weeks* Doxorubicine, Cyclosphosphamide Dactinomycine, Vincristine Alternating with Etoposide and Ifosfamide = experimental therapy * Local control at week 12: surgery and/or radiotherapy Holcombe EG et al., New Engl. J. Med, 2003, 348, 694
21 PNET tumours: : FACTS Holcombe EG et al., New Engl. J. Med, 2003, 348, 694
22 PNET tumours 5 year overall survival patients with metastases: 35 % (both arms) patients without metastases: standard arm: 61% exp- arm (etopophos/ifosf.) 72% p = 0.01 Prognostic unfavorable factors (5 year EFS): large tumour size (> 8 cm): 55 vs 75% p<0.001 tumor site (pelvis): 50 vs 61-68% p=0.003 age (> 18 years): 44 vs 60-70% p=0.001 gender (male): 59 vs 65% p=0.32 Holcombe EG et al., New Engl. J. Med, 2003, 348, 694
23 Case report 5 Case history: Woman, 37 years old Non smokers Healthy so far Fatigue since several weeks Loss of appetite Chest dyscomfort Lab. values: Hb, Lc, Tc normal Normal liver and kidney function α-foetoproteine / β HCG normal
24 Anterior-superior med. tumour Some calcification
25 Subtype of EGCT: Teratoma Mature teratomas (40% of EGCT) Well differentiated cells (2-3 layers) Females Diagnosis: incidental, slow growth CT: calcification (26%), fat, sebaceous material Surgery, no adjuvant therapy
26 Case report 6 Men, 24 years old Some cough, some thoracic dyscomfort Persistent feeling of something in the thorax Chest X Ray and CT scan
27 Case report 6 Tumor marker: β HCG: <3 α foetoprotein: Biopsy: Diagnosis: Teratocarcinoma, with yalk sac elements Carcinoma embryonale Extragonadal germ cell tumour
28 Case report 6 5 cycles of chemotherapy (BEP)
29 Extragonadal germ cell tumour FACTS Germ cell tumour: without any evidence of a primary tumor in testes or ovaries Frequency: 5% of GCT Gender: Men > women Young children: >50% extragonadal, sacrococcyx Risk factor: Klinefelter 47XXY Sites: Mediastinal Retroperitoneal Pineal, suprasellar Shivdasani RA et al., Principles and Practice of Genitourinary Oncology, Lippincott 1997
30 Extragonadal germ cell tumour Prognostic and predictive factors Site: poorest localisation Mediastinal Histologies: best prognosis have Seminomas Mature mediastinal teratomas (surgery alone) Age: better prognosis Children < 12 years Association with leukemia megacaryocitic disorder same cytogenetic alteration risk 6% McAleer JJ et al., Eur. J. Cancer 1992, 28A, 825 Marina N et al., J. Clin. Oncol. 2006, 24, 2544 Hartmann JT et al., Ann. Oncol. 2002, 13, 1017
31 Pathogenesis of EGCT Hypotheses Primordial germ cells fail to complete the normal migration along the urogenital ridge to the gonadal ridges during embryonal development Cells in the testes undergo reverse migration EGCT and GCT share a common cell of origin Glenn OA et al., Pediatr. Neurosurg. 1996, 24, 242 Chaganti RS et al., Cancer Res., 2000, 60, 1475
32 Diagnosis of EGCT Tumour markers (AFP, beta HCG) (85% both or one of both) Testis/Retrop. Cytogenetic Isochromosome 12p (25-30%) Histologies Mediastinal β-hcg 74% 38% α-foetoprotein 51% 74% Bokemeyer C et al., J. Clin. Oncol. 2002, 20, 1864 Genet P et al., Br. J. Haematol., 2000, 108, 885
33 Subtype EGCT: Seminoma Mediastinal seminomas (30%) Men years old For a long time asymptomatic (= large tumours) Risk of metastases very high
34 Subtype EGCT: Seminoma Therapy Exquisitely sensitive to RT and CT No large studies, recommendations based on small case studies (retrospective) Chemotherapy (BEP, VIP) preferred: 3-4 cycles Resection of tumor mass > 3 cm Retrospective study of patients with med./retroperitoneal seminomas (n=104) - Tumor characteristics: size 5 cm, 48% limited to mediastinum - Patients: med. age 33 years (18-65 years) - Chemotherapy: 3-4 cycles (according to Internat. Germ Cell Cancer Coll. Group) - Results: ORR: 92% OS rate a 5 years: 88% - Surgery: 25/104 (24%) = resection of remaining tumour: 2 (8%/2%) with vital seminoma or teratoma. Bokemeyer C et al., J. Clin. Oncol. 2002, 20, 1864
35 Subtype EGCT: NS-GCT
36 Subtype EGCT: NS-GCT NSGCT (20-30%) Mixture of tissue types: chorio-, terato-, embryonal carcinomas Men > females, years old Aggressive tumour: symptomatic Therapy: 4 cycles of BEP (or VIP in case of an intolerance to bleomycine)
37 Subtype EGCT: NS-GCT NSGCT (20-30%) Radical resection of residual masses Response: 20% CR (serologic and radiologic), after resection CR 50% Prognosis: long term survivors: 40-45% Salvage chemotherapy: unsuccessful, long term survival 0%
38 Management of EGCT: NS-GCT Chemotherapy 4-5 cycles of BEP Follow with tumor markers Surgery Remove mature Tissue Timing? If relapse: Chemotherapy High dose? Go for surgery if tumour markers are normal after 1-2 further chemotherapy cycles
39 Treatment outcome of patients with EGCT Type of tumor Number of pts ORR (%) Relapse rate (%) 5 year OS (%) Med. seminoma Retroperit. Seminoma Med. NS- EGCT Retroperit. NS-EGCT Bokemeyer C et al., J. Clin. Oncol. 2002, 20, 1864
40 Take home messages - Chemotherapy for mediastinal tumours: - lymphomas, PNET and teratocarcinomas - For teratocarcinomas: start chemotherapy - If tumor marker AFP, beta-hcg are elevated - And the situation is life threatening - For PNET and teratocarcinomas: multidisciplinary approach - After good response to chemotherapy => surgery (then if necessary: radiotherapy)
41 SAMO workshop on chest tumors Credits: Swiss Society of Medical Oncology: 10 credits Swiss Society of Surgery 10 credits Swiss Society of Pneumology: 10 credits Swiss Society of Radiotherapy: 10 credits Please fill out the questionnaire
42 SAMO workshops: SAMO 2008 Colon cancer April 2008 Breast cancer November 2008 Lucerne 2008
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