Salivary gland cancer - PDF Document

Presentation Transcript

  1. Salivary gland cancer Lisa Licitra Head and Neck Medical Oncology Unit Istituto Nazionale Tumori Milan, Italy

  2. DISCLOSURE OF INTEREST .

  3. Epidemiology of malignant tumors ? Malignant tumors: 1.31 /100,000/year (www.rarecare.eu) ? Equal sex distribution ? Average age = 47 yrs ? Risk factors = viruses, RT, occupation

  4. WHO 2005-2017 Acinic cell carcinoma Secretory carcinoma Mucoepidermoid carcinoma Adenoid cystic carcinoma Polymorphous (low-grade) adenocarcinoma Epithelial-myoepithelial carcinoma Clear cell carcinoma, NOS Basal cell adenocarcinoma Sebaceous adenocarcinoma (Sebaceous lymphadenocarcinoma) Cystadenocarcinoma (Low-grade cribriform cystadenocarcinoma) (Mucinous adenocarcinoma) Oncocytic carcinoma Salivary duct carcinoma Adenocarcinoma, NOS Myoepithelial carcinoma Carcinoma ex pleomorphic adenoma Carcinosarcoma (Metastatizing pleomorphic adenoma) Squamous cell carcinoma Undiff Carcinoma: Neuroendocrine and non endocrine Small cell carcinoma Large cell carcinoma Lymphoepithelial carcinoma ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ?

  5. Basaloid tumors Adenoid cystic ca Myoepithelial ca Epi-myoepithelial ca Pleomorphic adenoma Mucoepidermoid Salivary duct ca Adenocarcinoma Acinic cell ca Rare myoepthelial dediff Warthin’s Oncocytic tumors

  6. Badlani 2017

  7. Head and Neck Pathol 2009

  8. Treatment ? Optimal surgery: ? Gross total tumor resection ? Elective neck dissection is reserved for high grade and/or advanced-stage disease ? Facial nerve function preservation surgery whenever feasible ? PORT: ? High grade and/or advanced-stage disease ? R1 resections ? recurrent benign tumors ? Proton/carbonionRT: ? Unresectable/inoperable locoregional disease

  9. Shah: Head and Neck Surgery and Oncology, 3rdedition, 2003

  10. Shah: Head and Neck Surgery and Oncology, 3rdedition, 2003

  11. Laurie and Licitra JCO 2006

  12. Chemotherapy ? ACC ? RR = 5-22% ? median OS = 14-25 mos (monoCT) ? median OS = 8-67 mos (polyCT) ? Other histotypes ? RR = 30-40% ? median PFS = 6 mos (4-6)

  13. Chemotherapy ? Impact on OS: not yet demonstrated ? RR higher for local regional lesions ? Impact on QoL: possibile

  14. Issues ? Rare cancers ? Prognosis highly dependant on histology ? Chemosensitivity highly dependant on histology ? ACC: more resistant ? ADC: DOX, 5-FU, DDP, Taxol ? MEC: MTX + BLM

  15. Locati Oral Oncology 2009

  16. Locati Oral Oncology 2009

  17. Androgen receptor expression in SGCs and hormonal therapy 2 mos after ADT Licitra L et al, Ann Oncol 2003 Jaspers HCJ et al, J Clin Oncol 2011

  18. AdenoCa, 50 yrs old, AR + HER2 2+ Baseline CT scan baseline

  19. 4 months later

  20. Activity of ADT in SDC September 2017 March 2018

  21. September 2017 March 2018

  22. Jaspers HCJ et al, 2011

  23. IHC and androgen receptor expression AR overexpression Negative AR expression

  24. AR expression scoring system Head and Neck 2016

  25. Minimum 1% of AR positivity was considered

  26. Average 34% RR Int : 65% JPN: 41%

  27. Cisplatin + doxorubicin/ Carboplatin+paclitaxel Cohort A N° 76 Chemo-naive R N° 152 Androgen deprivation therapy Bicalutamide 50 mg daily + Triptorelin 3.75 q28days Relapsed/met AR overexpressing SDC AdenoCa Cohort B N° 76 Previously treated Androgen deprivation therapy AIMS - Cohort A: efficacy of ADT (PFS) in treatment naïve patients with recurrent and/or metastatic, androgen receptor (AR) expressing, SGCs. -Cohort B: response to ADT in pretreated patients with recurrent and/or metastatic, AR expressing SGCs.

  28. Generally, the AR nuclear immunostaining : showed strong intensity was in more than 70% of nuclei througout the sample Combined score: 3+ (high intensity); 3+ (≥ 70% of positive nuclei) = 6+ high High AR overexpression in a SDC

  29. AR negative expression was observed in oneAdenocarcinoma, NOS Combined score: 0 (negative intensity); + 0 (<10% of positive nuclei) = 0 negative negative AR expression in Adenocarcinoma, NOS

  30. Interestingly, in one case we observed a tight correlation between the lose ofAR immunorecativity and the acquisition of more anaplastic features of tumor cells Tumors cells with more anaplastic features: AR negative AR positive (high score) Tumor cells Decreasing ofAR immunodecoration paralles the increasing of anaplastic features of the tumor cells This case was enrolled asAR high.......

  31. Outside of EORTC1206: Occasionally, despite an omogenous morphology of the sample, the AR nuclear immunostaining modulates in terms of intensity: all the tumor nuclei are immunolabelled but the immunostaining intensity ranges from weak to strong We restricted the evaluation intensity: The intensity is always strong (3+) and the extent may vary from 1+ to 2+ of the AR score to the area exhibiting strong Area with weak intensity Area with high intensity SDC showing heterogenousAR immunoreactivity

  32. May 2012 March 2012 Phase II trial of abiraterone acetate in patients with relapsed and/or metastatic, castration resistant salivary gland cancers (NCT02867852)

  33. Molecular characterization of CTCs CTC-specific gene EPCAM MUC1 ERBB2 Amplicon size 395 299 265 i) CTC + Expression ng/µl 2.57 1.09 0.79 CTC status threshold definedin HD 0.40ng/µL 0.10ng/ µL 0.20ng/µL CTC status pos pos pos CRPC patients treated with enzalutamide /abiraterone: ii) CTC+ and ARv7 + ARv7 expression 77copies/mL blood PD : median 35.5 copies/mL blood PR+SD: median 0 copies/mL blood iii) CTC+ and ARv7+ and full lenght AR+ CRPC patients treated with enzalutamide /abiraterone: AR-full length expression 344 copies/mL blood PD : median 436.5 copies/mL blood PR+SD: median 0 copies/mL blood Ann Oncol in press

  34. SDC Method of analysis Clinical role IHC PCR Western blotting FISH NGS AR > 80% 50% male 26.6% female (splice variants) 44% male 27% female 50% AR-V7 Diagnostic/ Prognostic? HER2 30-44% - - 30-50% Prognostic? EGFR 38% - - 25% EGFR polisomy (gene amplificationnot reported) - TRK-A 67% PIK3CA - 19-33% - - 23% - BRAF/HRAS /NF1 - - - 74% -

  35. Salivary duct carcinoma with NCOA-RET fusion responding to Cabozantinib Wang, Clin Can Res 2016