Head & Neck cancers  Lisa Licitra  Istituto Nazionale Tumori  Milano
Rare: incidence  <  6/100.000 <ul><li>Nasopharyngeal cancer 0.44 </li></ul><ul><li>Nasal cavity and sinuses 0.44 </li></ul...
Sinonasal tumors <ul><li>Maxillary sinus  60% </li></ul><ul><li>Ethmoid sinus 10-15% </li></ul><ul><li>Frontal sinus 1% </...
WHO 2005 <ul><li>Squamous cell carcinoma (SCC) </li></ul><ul><li>Lymphoepithelial carcinoma </li></ul><ul><li>Adenocarcino...
Frierson Am J Surg Pathol 1986 Ejaz Adv Anat Pathol 2005 Feature ENB SNUC SNEC Prognosis Necrosis Nuclear anaplasia Mitose...
 
Dulgerov Cancer 2001
 
Head & Neck 2005
Ganly, Head & Neck 2005
Ganly, Head & Neck 2005
Arch Otolaryngol H&N Surgery 2009
 
Hematol Oncol Clin North Am 2008
 
 
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 (...
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 Risch...
Dulgerov Lancet Oncology 2001
Head & Neck 2008
 
 
 
Arch Otolaryngol Head and Neck Surg, 2001
Hanna Arch Otolaryngol H&N Surg 2011
 
 
Conclusions <ul><li>WHO classification </li></ul><ul><li>Multimodal therapeutic approach that includes surgery, radiation ...
 
IARC 2009
Etiologic heterogeneity of OSCCs Adapted from Gillison ML. Seminars in Oncology, 2004 HPV-induced OSCCs Tobacco/alcohol-in...
Smeets SJ Oncogene 2006
JNCI, 2000
HPV as a prognostic factor Gillison, JNCI 2000
HPV in H&N cancer:  systematic review   Kreimer A, 2005
 
HPV-R HPV-U
Hematol Oncol Clin N Am 2008
Risk factors HPV + SCC <ul><li>Sexual behaviour </li></ul><ul><li>HPV exposure </li></ul><ul><li>Marijuana consumption </l...
Oral Oncology 2007
HPV pos H&N and stage…   Study N pts Subsite % HPV Advanced stage for HPV + Gillison, 00 252 H&N 25 not relevant (N) Melli...
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, ...
 
 
RTOG 0129 <ul><li>SFRT+ CDDP x 3  </li></ul><ul><li>AFX-c + CDDP x 2 </li></ul><ul><li>433/721 Oropharynx </li></ul><ul><l...
Ang K NEJM 2010
 
22% vs 43% 38% vs 30% 40% vs 27%
 
Fisher CA Annals Oncol 2010
 
Gold standard (?)  tumor HPV detection <ul><li>Traditional PCR too sensitive </li></ul><ul><li>Quantitative viral DNA or m...
P16 positive tumors  HPV + HPV - ANG KK 2010
 
P16 neg =15 pts  5 non funct mut;  3 overexpr EGFR; overexp cyclin D1;  1 PI3KA mut; 1 gene copy number
R&M: OS as function of HPV positivity 24 pts 72 pts
Clinical trial strategies <ul><li>Different therapeutic options for HPV+ and HPV- oropharyngeal SCCs  </li></ul><ul><li>Am...
WHO 2005 <ul><li>Acinic cell carcinoma </li></ul><ul><li>Mucoepidermoid carcinoma </li></ul><ul><li>Adenoid cystic carcino...
High risk tumors … <ul><li>SDC  </li></ul><ul><li>MCC: grading </li></ul><ul><li>ACC: staging (bone),  hist. pattern (soli...
TREATMENT  <ul><li>Optimal surgery :  </li></ul><ul><li>Gross total tumor resection  </li></ul><ul><li>Elective neck disse...
Schulz-Ertner D Cancer 2005 ACC  RT + Carbonion RT
Lung metastasectomy in ACC : selection criteria  <ul><li>R0 resection  </li></ul><ul><li>< 6 metastases </li></ul><ul><li>...
Locati L 2005 OS FFP OS
Laurie & Licitra J Clin Oncol 2006
<ul><li>Impact on OS not yet demonstrated </li></ul><ul><li>RR > at localregional level  </li></ul><ul><li>Impact on QoL p...
Locati  L Oral Oncology 2009
Biological agents in  recurrent/mts SGCs Author Study PTS Treatment Outcome Glisson 05 Ph II 29 Gefitinib 250 RR 0 Agulnik...
HORMONAL TREATMENT IN RELAPSED  AR-EXPRESSING   PAROTID ADENOCARCINOMA  At treatment beginning…… Two months later…..
2010
A J Surg Pathol 2010
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Solid Cancers: An Introduction - Slide 6 - L. Licitra - Rare cancers of head and neck

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Solid Cancers: An Introduction - Slide 6 - L. Licitra - Rare cancers of head and neck

  1. 1. Head & Neck cancers Lisa Licitra Istituto Nazionale Tumori Milano
  2. 2. Rare: incidence < 6/100.000 <ul><li>Nasopharyngeal cancer 0.44 </li></ul><ul><li>Nasal cavity and sinuses 0.44 </li></ul><ul><li>Salivary gland cancers 1.31 </li></ul><ul><li>Oropharyngeal cancer 2.75 </li></ul><ul><li>Oral cavity 4.79 </li></ul>
  3. 3. Sinonasal tumors <ul><li>Maxillary sinus 60% </li></ul><ul><li>Ethmoid sinus 10-15% </li></ul><ul><li>Frontal sinus 1% </li></ul><ul><li>Sphenoid sinus 1% </li></ul><ul><li>Nasal cavities 20-30% </li></ul>
  4. 4. WHO 2005 <ul><li>Squamous cell carcinoma (SCC) </li></ul><ul><li>Lymphoepithelial carcinoma </li></ul><ul><li>Adenocarcinoma </li></ul><ul><li>ITAC, non ITAC (tubulopapillary LG) </li></ul><ul><li>Salivary gland type carcinomas </li></ul><ul><li>Neuroendocrine tumours </li></ul><ul><li>carcinoid, small cell neuroendocrine type </li></ul><ul><li>Sinonasal undifferentiated carcinoma (SNUC) (HPV 10%)* </li></ul>El-Mofty Am J Surg Pathol 2005
  5. 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
  7. 9. Head & Neck 2005
  8. 10. Ganly, Head & Neck 2005
  9. 11. Ganly, Head & Neck 2005
  10. 12. Arch Otolaryngol H&N Surgery 2009
  11. 14. Hematol Oncol Clin North Am 2008
  12. 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
  13. 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
  14. 19. Dulgerov Lancet Oncology 2001
  15. 20. Head & Neck 2008
  16. 24. Arch Otolaryngol Head and Neck Surg, 2001
  17. 25. Hanna Arch Otolaryngol H&N Surg 2011
  18. 28. Conclusions <ul><li>WHO classification </li></ul><ul><li>Multimodal therapeutic approach that includes surgery, radiation and histotype driven chemotherapy </li></ul><ul><li>Biology to be exploited </li></ul>
  19. 30. IARC 2009
  20. 31. Etiologic heterogeneity of OSCCs Adapted from Gillison ML. Seminars in Oncology, 2004 HPV-induced OSCCs Tobacco/alcohol-induced OSCCs
  21. 32. Smeets SJ Oncogene 2006
  22. 33. JNCI, 2000
  23. 34. HPV as a prognostic factor Gillison, JNCI 2000
  24. 35. HPV in H&N cancer: systematic review Kreimer A, 2005
  25. 37. HPV-R HPV-U
  26. 38. Hematol Oncol Clin N Am 2008
  27. 39. Risk factors HPV + SCC <ul><li>Sexual behaviour </li></ul><ul><li>HPV exposure </li></ul><ul><li>Marijuana consumption </li></ul>
  28. 40. Oral Oncology 2007
  29. 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)
  30. 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
  31. 45. RTOG 0129 <ul><li>SFRT+ CDDP x 3 </li></ul><ul><li>AFX-c + CDDP x 2 </li></ul><ul><li>433/721 Oropharynx </li></ul><ul><li>323 HPV determination </li></ul><ul><li>198 HPV 16 + </li></ul><ul><li>ISH & p16 IHC </li></ul>
  32. 46. Ang K NEJM 2010
  33. 48. 22% vs 43% 38% vs 30% 40% vs 27%
  34. 50. Fisher CA Annals Oncol 2010
  35. 52. Gold standard (?) tumor HPV detection <ul><li>Traditional PCR too sensitive </li></ul><ul><li>Quantitative viral DNA or mRNA PCR more precise </li></ul><ul><li>ISH not completely sensitive </li></ul><ul><li>p16 is a surrogate marker </li></ul>
  36. 53. P16 positive tumors HPV + HPV - ANG KK 2010
  37. 55. P16 neg =15 pts 5 non funct mut; 3 overexpr EGFR; overexp cyclin D1; 1 PI3KA mut; 1 gene copy number
  38. 56. R&M: OS as function of HPV positivity 24 pts 72 pts
  39. 57. Clinical trial strategies <ul><li>Different therapeutic options for HPV+ and HPV- oropharyngeal SCCs </li></ul><ul><li>Among HPV + risk based enrolment </li></ul><ul><li>Need for HPV detection standardisation </li></ul>
  40. 58. WHO 2005 <ul><li>Acinic cell carcinoma </li></ul><ul><li>Mucoepidermoid carcinoma </li></ul><ul><li>Adenoid cystic carcinoma </li></ul><ul><li>Polymorphous low-grade adenocarcinoma </li></ul><ul><li>Epithelial-myoepithelial carcinoma </li></ul><ul><li>Clear cell carcinoma, NOS </li></ul><ul><li>Basal cell adenocarcinoma </li></ul><ul><li>Sebaceous carcinoma </li></ul><ul><li>Sebaceous lymphadenocarcinoma </li></ul><ul><li>Cystadenocarcinoma </li></ul><ul><li>Low-grade cribriform cystadenocarcinoma </li></ul><ul><li>Mucinous adenocarcinoma </li></ul><ul><li>Oncocytic carcinoma </li></ul><ul><li>Salivary duct carcinoma </li></ul><ul><li>Adenocarcinoma, NOS </li></ul><ul><li>Myoepithelial carcinoma </li></ul><ul><li>Carcinoma ex pleomorphic adenoma </li></ul><ul><li>Carcinosarcoma </li></ul><ul><li>Metastatizing pleomorphic adenoma </li></ul><ul><li>Squamous cell carcinoma </li></ul><ul><li>Small cell carcinoma </li></ul><ul><li>Large cell carcinoma </li></ul><ul><li>Lymphoepithelial carcinoma </li></ul><ul><li>Sialoblastoma </li></ul>
  41. 59. High risk tumors … <ul><li>SDC </li></ul><ul><li>MCC: grading </li></ul><ul><li>ACC: staging (bone), hist. pattern (solid component > 30%), surg margins </li></ul><ul><li>AdC: grading </li></ul><ul><li>MC: grading </li></ul><ul><li>Acinic Cell C: submandibular origin, staging </li></ul><ul><li>EMC recurrence 40% </li></ul>
  42. 60. TREATMENT <ul><li>Optimal surgery : </li></ul><ul><li>Gross total tumor resection </li></ul><ul><li>Elective neck dissection is reserved for high grade and/or advanced-stage disease </li></ul><ul><li>Facial nerve function preservation surgery whenever feasible </li></ul><ul><li>PORT is reserved for high grade and/or advanced-stage disease, R1 resections, recurrent benign tumors </li></ul><ul><li>Unresectable/inoperable locoregional disease hadrotherapy is promising </li></ul>
  43. 61. Schulz-Ertner D Cancer 2005 ACC RT + Carbonion RT
  44. 62. Lung metastasectomy in ACC : selection criteria <ul><li>R0 resection </li></ul><ul><li>< 6 metastases </li></ul><ul><li>DFI > 36 months </li></ul>
  45. 63. Locati L 2005 OS FFP OS
  46. 64. Laurie & Licitra J Clin Oncol 2006
  47. 65. <ul><li>Impact on OS not yet demonstrated </li></ul><ul><li>RR > at localregional level </li></ul><ul><li>Impact on QoL possibile </li></ul>Results of chemo …
  48. 66. Locati L Oral Oncology 2009
  49. 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
  50. 68. HORMONAL TREATMENT IN RELAPSED AR-EXPRESSING PAROTID ADENOCARCINOMA At treatment beginning…… Two months later…..
  51. 69. 2010
  52. 70. A J Surg Pathol 2010

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