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Solid Cancers: An Introduction - Slide 6 - L. Licitra - Rare cancers of head and neck
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  • 1. Head & Neck cancers Lisa Licitra Istituto Nazionale Tumori Milano
  • 2. Rare: incidence < 6/100.000
    • Nasopharyngeal cancer 0.44
    • Nasal cavity and sinuses 0.44
    • Salivary gland cancers 1.31
    • Oropharyngeal cancer 2.75
    • Oral cavity 4.79
  • 3. Sinonasal tumors
    • Maxillary sinus 60%
    • Ethmoid sinus 10-15%
    • Frontal sinus 1%
    • Sphenoid sinus 1%
    • Nasal cavities 20-30%
  • 4. WHO 2005
    • Squamous cell carcinoma (SCC)
    • Lymphoepithelial carcinoma
    • Adenocarcinoma
    • ITAC, non ITAC (tubulopapillary LG)
    • Salivary gland type carcinomas
    • Neuroendocrine tumours
    • carcinoid, small cell neuroendocrine type
    • Sinonasal undifferentiated carcinoma (SNUC) (HPV 10%)*
    El-Mofty Am J Surg Pathol 2005
  • 5. Frierson Am J Surg Pathol 1986 Ejaz Adv Anat Pathol 2005 Feature ENB SNUC SNEC Prognosis Necrosis Nuclear anaplasia Mitoses Vascular invasion Secretory granules Keratin S100 NSE variable + + variable ++ +++ + ++ +++ poor +++ +++ +++ +++ + +++ - variable favorable - - variable NR +++ ++ ++ +++
  • 6.  
  • 7. Dulgerov Cancer 2001
  • 8.  
  • 9. Head & Neck 2005
  • 10. Ganly, Head & Neck 2005
  • 11. Ganly, Head & Neck 2005
  • 12. Arch Otolaryngol H&N Surgery 2009
  • 13.  
  • 14. Hematol Oncol Clin North Am 2008
  • 15.  
  • 16.  
  • 17. SNUC Author N pts treatment outcome Levine 87 11 RT + CT 90% DOD Deutsch 93 6 CT > S (50%) + RT 33% DOD Righi 96 7 S (50%) + RT + CT 60% DOD Gorelick 00 4 S (100%) + RT + CT 90% DOD Kim 04 8 S (50%) + RT + CT 75% DOD Kramer 04 4 S (100%) + RT + CT 0 % DOD Chen 08 21 S (90%) + RT + CT 57 % DOD
  • 18. 40% DOD S + RT or RT + CT 15 Tanzler 08 65% DOD CT+ RT + S or CT + RT 20 Musy 02 40% DOD CT + RT/CT or S + RT/CT 10 Rischin 04 62,5% 5yr OS S (50%) + RT + CT or CT + S or RT 16 Rosenthal 04 50% DOD S + RT + CT 14 Miyamoto 00 outcome treatment N pts Author
  • 19. Dulgerov Lancet Oncology 2001
  • 20. Head & Neck 2008
  • 21.  
  • 22.  
  • 23.  
  • 24. Arch Otolaryngol Head and Neck Surg, 2001
  • 25. Hanna Arch Otolaryngol H&N Surg 2011
  • 26.  
  • 27.  
  • 28. Conclusions
    • WHO classification
    • Multimodal therapeutic approach that includes surgery, radiation and histotype driven chemotherapy
    • Biology to be exploited
  • 29.  
  • 30. IARC 2009
  • 31. Etiologic heterogeneity of OSCCs Adapted from Gillison ML. Seminars in Oncology, 2004 HPV-induced OSCCs Tobacco/alcohol-induced OSCCs
  • 32. Smeets SJ Oncogene 2006
  • 33. JNCI, 2000
  • 34. HPV as a prognostic factor Gillison, JNCI 2000
  • 35. HPV in H&N cancer: systematic review Kreimer A, 2005
  • 36.  
  • 37. HPV-R HPV-U
  • 38. Hematol Oncol Clin N Am 2008
  • 39. Risk factors HPV + SCC
    • Sexual behaviour
    • HPV exposure
    • Marijuana consumption
  • 40. Oral Oncology 2007
  • 41. HPV pos H&N and stage… Study N pts Subsite % HPV Advanced stage for HPV + Gillison, 00 252 H&N 25 not relevant (N) Mellin, 00 34 oroph 41 not relevant (stage) Schwartz, 01 254 H&N 15 for N and stage Lindel, 01 99 oroph 14 not relevant (T and N) Ritchie, 03 128 oral + oroph 21 for stage IV Weinberger, 06 79 oroph 61 for N (HPV + p16) Licitra, 06 90 oroph 19 not relevant (stage)
  • 42. HPV-pos H&N cause-specific survival Study N pts Subsite % HPV TX HR Gillison, 00 252 H&N 25 Surg and/or RT 0.40 Mellin, 01 34 oroph 41 RT (100%) + Surg (45%) 0.50 Schwartz, 01 254 H&N 15 Surg and/or RT 0.17 Lindel, 01 99 oroph 14 RT + CT 0.35 Ritchie, 03 128 oral + oroph 21 Surg and/or RT 0.30 Weinberger, 06 79 oroph 61 RT (100%) + Surg (40 %) ------ Licitra, 06 90 oroph 19 Surg (100%) + RT (66%) 0.26
  • 43.  
  • 44.  
  • 45. RTOG 0129
    • SFRT+ CDDP x 3
    • AFX-c + CDDP x 2
    • 433/721 Oropharynx
    • 323 HPV determination
    • 198 HPV 16 +
    • ISH & p16 IHC
  • 46. Ang K NEJM 2010
  • 47.  
  • 48. 22% vs 43% 38% vs 30% 40% vs 27%
  • 49.  
  • 50. Fisher CA Annals Oncol 2010
  • 51.  
  • 52. Gold standard (?) tumor HPV detection
    • Traditional PCR too sensitive
    • Quantitative viral DNA or mRNA PCR more precise
    • ISH not completely sensitive
    • p16 is a surrogate marker
  • 53. P16 positive tumors HPV + HPV - ANG KK 2010
  • 54.  
  • 55. P16 neg =15 pts 5 non funct mut; 3 overexpr EGFR; overexp cyclin D1; 1 PI3KA mut; 1 gene copy number
  • 56. R&M: OS as function of HPV positivity 24 pts 72 pts
  • 57. Clinical trial strategies
    • Different therapeutic options for HPV+ and HPV- oropharyngeal SCCs
    • Among HPV + risk based enrolment
    • Need for HPV detection standardisation
  • 58. WHO 2005
    • Acinic cell carcinoma
    • Mucoepidermoid carcinoma
    • Adenoid cystic carcinoma
    • Polymorphous low-grade adenocarcinoma
    • Epithelial-myoepithelial carcinoma
    • Clear cell carcinoma, NOS
    • Basal cell adenocarcinoma
    • Sebaceous carcinoma
    • 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
    • Small cell carcinoma
    • Large cell carcinoma
    • Lymphoepithelial carcinoma
    • Sialoblastoma
  • 59. High risk tumors …
    • SDC
    • MCC: grading
    • ACC: staging (bone), hist. pattern (solid component > 30%), surg margins
    • AdC: grading
    • MC: grading
    • Acinic Cell C: submandibular origin, staging
    • EMC recurrence 40%
  • 60. 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 is reserved for high grade and/or advanced-stage disease, R1 resections, recurrent benign tumors
    • Unresectable/inoperable locoregional disease hadrotherapy is promising
  • 61. Schulz-Ertner D Cancer 2005 ACC RT + Carbonion RT
  • 62. Lung metastasectomy in ACC : selection criteria
    • R0 resection
    • < 6 metastases
    • DFI > 36 months
  • 63. Locati L 2005 OS FFP OS
  • 64. Laurie & Licitra J Clin Oncol 2006
  • 65.
    • Impact on OS not yet demonstrated
    • RR > at localregional level
    • Impact on QoL possibile
    Results of chemo …
  • 66. Locati L Oral Oncology 2009
  • 67. Biological agents in recurrent/mts SGCs Author Study PTS Treatment Outcome Glisson 05 Ph II 29 Gefitinib 250 RR 0 Agulnik 06 Licitra 06 Hotte 05 Ph II Ph II Ph II 38 30 16 Lapatinib 1500 Cetuximab Imatinib 400 RR 0 RR 0 RR 0 Pfeffer 06 Argiris 06 Ph II Ph II 10 25 Imatinib 400 - 800 Bortezomib RR 0 RR 0
  • 68. HORMONAL TREATMENT IN RELAPSED AR-EXPRESSING PAROTID ADENOCARCINOMA At treatment beginning…… Two months later…..
  • 69. 2010
  • 70. A J Surg Pathol 2010