1. Head & Neck Ca. (Epithelial tumors) Mohamad KADRI. MD. Clinical oncology. Medical director of AlBerouni University Hospital President of Syrian Association of Oncology (SAO)

2. Head and neck cancer In 2014, more than 55000 new cases were diagnosed (3% of new cancer cases in USA). > 90% SCC… Alcohol, tobacco, and HPV, are now well accepted risk factors… NCCN Clinical Practice Guidelines in Oncology: Head & Neck Cancer, v.1. 2015

3. 1- Head and neck epithelial ca (Nasopharyngeal Ts are not included)  Tis,T1, T2 and N0 : - Surgery +/- RT. - RT.  T3,T4, or N+ : - Surgery then RT or chemo/RT. - RT or chemo/RT, then surgery. - RT or chemo/RT.  T any N any (maxill): Surgery and/or RT and/or Chemo/RT NCCN Clinical Practice Guidelines in Oncology: Head & Neck Cancer, v.1. 2015

4. Concomitant chemo/RT  CDDP 75-100 mg/m2, q3 wks. or 40-50 mg/m2, weekly.  CDDP 75-100 mg/ m2, d1, q3wks. Fu 750-1000 mg/m2, d1-d4(5), q3wks.  CDDP 20 mg/m2, d1-d5, q4wks. Fu 200 mg/m2, d1-d5, q4wks.  CBDCA 70 mg/m2, d1-d5, q3-4wks. Fu 600 mg/m2, d1-d5, q3-4wks.  - CDDP or CBDCA + Paclitaxel. NCCN Clinical Practice Guidelines in Oncology: Head & Neck Cancer, v.1. 2015

5. Concomitant Cetuximab/RT  Cetuximab + RT: - SCC. Cetuximab (EGFR-antibody) is the 1 st targeted therapy approved for the treatment of HNSCC. - Head and neck, (Non-Nasopharyngeal). - concomitant with RT as definitive treatment.  Cetuximab + RT: - 400 mg/m2, 2h inf, 1week before RT. - 250 mg/m2, 1h inf, weekly for 7wks starting with RT. NCCN Clinical Practice Guidelines in Oncology: Head & Neck Cancer, v.1 2015

6. Concomitant Cetuximab/RT Cetuximab + RT: Cetuximab + RT, is equal to CDDP + RT, and better than RT alone, (by 5.5% 3years OS), but without increase of toxicity. Cetuximab, can be considered an alternative to chemo for unfit patients to chemotherapy. (FDA approval) Cetuximab + chemotherapy + RT, Not routinely recommended now, due to toxicity. NCCN Clinical Practice Guidelines in Oncology: Head & Neck Cancer, v.1 2015

7. 2- Nasopharynx  T1 N0 : definitive RT.  T2,3,4 and/or N+ : - CDDP 100 mg/m2, d1,22,43, or 40 mg/m2, weekly, during RT, followed by: - CDDP 80 mg/m2, d1, q3wks, 3cycles. - Fu 1000 mg/m2, d1-d4, q3wks, 3cycles. NCCN Clinical Practice Guidelines in Oncology: Head & Neck Cancer, v.1. 2015

8. Induction chemotherapy +/- Cetuximab

9. The standard chemoradiotherapy approach for fit patients with locally advanced disease remains concurrent CDDP and RT. Induction chemotherapy is not considered standard treatment in advanced disease. ESMO Guidelines. Head & Neck Cancer. NCCN Clinical Practice Guidelines in Oncology: Head & Neck Cancer, v.1 2015

10. Induction chemotherapy +/- Cetuximab 1- Not approved as standard of care. 2- No significant survival benefit. 3- Category 3 for Nasopharyngeal ca.. 4- May be suitable, (as optional), for some cases. NCCN Clinical Practice Guidelines in Oncology: Head & Neck Cancer, v.1 2015

11. Induction chemotherapy (optional) 2-3 cycles Organ preservation plan. (total laryngectomy required) Very advanced H&N ca,(primary or nodes) excluded from primary surgery. NCCN Clinical Practice Guidelines in Oncology: Head & Neck Cancer, v.1 2015

12. Induction chemotherapy (optional) 2-3 cycles Organ preservation plan. (total laryngectomy required) Very advanced H&N ca,(primary or nodes) excluded from primary surgery. NCCN Clinical Practice Guidelines in Oncology: Head & Neck Cancer, v.1 2015

13. Induction chemotherapy (optional) 2-3 cycles (organ preservation plan) 1- Hypopharynx, or supraglottic larynx, selected T1-2- 3 any N (total laryngectomy required). 2- Glottic larynx, T3 any N (total laryngectomy required). 3- Hypopharynx, supraglottic, or glottic larynx, T4a any N, (refuse primary surgery). NCCN Clinical Practice Guidelines in Oncology: Head & Neck Cancer, v.1. 2015

14. Induction chemotherapy (optional) 2-3 cycles (organ preservation plan) 2-3 cycles induction chemotherapy, then re- staging: - CR or PR in primary site chemo/RT, followed by surgery to residuals. - Less than PR in primary site surgery, followed by RT or chemo/RT. NCCN Clinical Practice Guidelines in Oncology: Head & Neck Cancer, v.1. 2015

15. Induction chemotherapy (optional) 2-3 cycles Organ preservation plan. (total laryngectomy required) Very advanced H&N ca,(primary or nodes) excluded from primary surgery. NCCN Clinical Practice Guidelines in Oncology: Head & Neck Cancer, v.1. 2015

16. Induction chemotherapy (optional) 2-3 cycles 1- Oropharynx, T3-4 and/or N2-3, excluded from primary surgery. 2- Very advanced H&N ca,(primary or nodes) Induction CT, then RT or chemo/RT, followed by surgery or follow up. (increase locoregional/systemic control). NCCN Clinical Practice Guidelines in Oncology: Head & Neck Cancer, v.1. 2015

17. Induction chemotherapy(optional) 2-3 cycles PF: - CDDP 75-100 mg/m2 d1, q3wks. - Fu 750-1000 mg/m2 d1-4(5), q3wks. TPF : - Docetaxel 75 mg/m2 d1, q3wks. - CDDP 75-100 mg/m2 d1, q3wks. - Fu 750-1000 mg/m2 d1-4(5), q3wks. PPF: - Paclitaxel 175 mg/m2, d1, q3-4wks. - CDDP 60 mg/m2 d1, q3-4wks. - Fu 750-1000 mg/m2 d1-4(5), q3wks. NCCN Clinical Practice Guidelines in Oncology: Head & Neck Cancer, v.1. 2015

18. Induction chemotherapy…. CDDP-based induction chemotherapy followed by high dose q3w CDDP chemoradiotherapy is not recommended now due to toxicity concerns… After induction chemotherapy, multiple options can be used for the RT-based chemoradiation portion of therapy, RT alone, weekly carboplatin, cetuximab, and weekly CDDP for Nasopharyngeal ca.

19. Recurrent, resistant, or metastatic disease Single agent: - Bleomycin. - MTX. - FU. - Docetaxel. -Paclitaxel. - CDDP. - CBDCA. - Capecitabine. -Gemcitabine. (Nasopharyngeal ca. only) -Venorelbine. (Non-Nasopharyngeal ca) -Cetuximab. (Non-Nasopharyngeal ca) NCCN Clinical Practice Guidelines in Oncology: Head & Neck Cancer, v.1. 2015

20. Recurrent, resistant, or metastatic disease Combination chemotherapy :  CDDP or Carboplatin + 5-Fu.  Docetaxel + CDDP + Fu.  CDDP + Epirubicin + Bleomycin. (Nasopharyngeal only)  Paclitaxel or Docetaxel + CDDP or CBDCA.  CDDP + Paclitaxel or Docetaxel + Cetuximab. (Non-nasopharyngeal)  CDDP or CBDCA + Paclitaxel + Ifosfamide.  Ifosfamide + Folinic acid + Fu. (Nasopharyngeal only)  Gemcitabine + CDDP. (Nasopharyngeal only)  CDDP or Carboplatin + 5-Fu + Cetuximab. (Non-nasopharyngeal)  CDDP + Cetuximab. (Non-nasopharyngeal)  Carboplatin + Cetuximab. (Nasopharyngeal only)  Gemcitabine + Venorelbine. (Nasopharyngeal only)  CDDP + Mitoxantrone. (salivary glands Ts.)  CDDP + Doxorubicin. (salivary glands Ts.) NCCN Clinical Practice Guidelines in Oncology: Head & Neck Cancer, v.1. 2015

21. Radiation therapy technique

22. FIRST CURE OF CANCER BY X-RAYS 1899 - BASAL CELL CARCINOMA X-rays were used to cure cancer very soon after their discovery

23. The first patient received radiation therapy from the medical linear accelerator Stanford 2-year-old boy with retinoblastoma

25. Head and Neck Immobilization devices

26. Organs at Risk

27. PTV (70 Gy) = GTV (70)+ 1cm

28. PTV (54-60 Gy) = CTV(54-60)+1cm

29. Organs at Risk-DVH Cord max < 45 Gy. Brainstem max < 54 Gy. Optic nerves max < 50 Gy. Optic Chiasm max < 50 Gy. Retina max < 45 Gy. Target mean = 70 Gy, +/-5%. Non-involved tissue minimize.

30. Fields Setup

31. L - Nodes (AP - PA)

32. R - Nodes (AP - PA)

33. PTV – primary tumor (70 Gy)

34. PTV - Node (70 Gy)

35. Plan Sum

36. Dose Volume Histogram

38. Advanced computerization and Hardware control and processing. Advanced radiation safety devices MLC Multileaf collimator

39. Lateral Isocenter Verification Portal Imaging

41. Thank you Mohamad KADRI. MD. Clinical oncology. Medical director of AlBerouni University Hospital President of Syrian Association of Oncology (SAO)