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Head and Neck

Head and Neck. By Dr. Adel Gabr SECI.,2012. Outline. Introduction Staging Who needs multimodality treatment Incorporate chemotherapy to definitive local tx Adjuvant Induction Concurrent Organ preservation Laryngeal cancer as an example. Introduction. Head and neck cancer.

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Head and Neck

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  1. Head and Neck By Dr. Adel Gabr SECI.,2012

  2. Outline • Introduction • Staging • Who needs multimodality treatment • Incorporate chemotherapy to definitive local tx • Adjuvant • Induction • Concurrent • Organ preservation • Laryngeal cancer as an example

  3. Introduction

  4. Head and neck cancer • Heterogeneous disease • Oral cavity, oropharynx, larynx, hypopharynx • Mostly SCC • Common etiology: smoking and drinking (betel nut for oral ca) • Similar biological behavior • Today’s topic • Nasopharynx: • WHO class type III: undifferentiate ca (NPC) • Nasal and paranasal sinus • Salivary gland

  5. Anatomy

  6. Staging

  7. Generally, T stage • Depends on anatomical location, complicate • General concept of T stage • T1, T2: confined, not invade adjacent tissue • T3: larger, may invade adjacent tissue • T4: deeply invade adjacent tissue/organ • 4a, 4b: depends on extend of invasion • Critical structure: skull base, pre-veterbral fascia, internal carotid artery, mediastinum

  8. T stage of oropharyngeal cancer T1 T2 T3 Invade to adjacent tissue, more extensive T4a T4b Invade to adjacent tissue, less extensive

  9. N1 Single ipsilateral, < 3cm Single,< 3 cm Ipsilateral Contralateral

  10. Single,3-6 cm Contralateral Ipsilateral N2a Single ipsilateral, 3-6cm

  11. Contralateral N2b Multiple ipsilateral, < 6cm < 6 cm Ipsilateral

  12. Contralateral N2c Bilateral or contralateral, < 6cm < 6 cm Ipsilateral

  13. Contralateral N3 Any LN > 6cm > 6 cm Ipsilateral

  14. Staging - (Early)

  15. Staging (Adnvnced)

  16. Management of SCCHN Early stage Stage I, II Locoregionallyadvanced Stage III, IVA, B Metastatic stage (IVC) or Recurrent Resectable 1st L CT (mainly cis) Evaluation of treatment goals Organ Preservation? Performance Status (PS)? Patient preference No Yes 2nd L CT or Erbitux Evaluation of treatment goals Organ Preservation? PS? Patient preference Surgery Radiation therapy (RT) PS Surgery and pathology review • Concurrent CT + RT: • RT + Erbitux • RT + CT (lower doses) • RT single modality • Concurrent CT + RT: • RT + cisplatin CT • RT + Erbitux Intermediate risk Low risk <1 +ve LN No ECE High risk >2 +ve LN &/or ECE Planned Neck Dissection RT Disease Progression – go to recurrent setting

  17. Resectability, Surgery • Depends on T stage : • T1, T2: resectable • T3: may be resectable • T4: mostly unresectable • Depends on surgical team • Wide excision  reconstruction • ENT surgeon  plastic surgeon • Depends on patients • Organ preservation

  18. Definitive local therapy • Historically • Resectable: surgery +/- RT • Primary tumor: margin positive or close, perineural invasion, vascular embolism • LN: multiple, extracapsular extension • Unresectable: RT alone • Incorporate chemotherapy into local therapy • PF in 1st line: RR 70-90%, CR 15-30%

  19. Chemotherapy

  20. Incorporation of chemotherapy • Before definitive treatment: • Induction/neoadjuvant chemotherapy • After definitive treatment • Adjuvant/consolidation chemotherapy • Concurrent with radiotherapy • Concurrent chemoradiotherapy

  21. Adjuvant chemotherapy

  22. Intergroup 0034 Cisplatin 100mg/m2, D1 5-FU 1000mg/m2/d IVF 24hrs, D1-D5 q3w Surgery C/T x 3 XRT 442 pts, resectable, III/IV, SCC Compliance of adjuvant C/T: 63% Surgery XRT Laramore GE et al. Int J Radiat Oncol Biol Phys 1992; 23: 705-713

  23. NCI A Surgery XRT Compliance:9% complete 6 cycles27% complete > 3 cycles45% received none 443 pts, resectable, III/IV, SCC B C/T x 1 Surgery XRT C C/T x 1 Surgery XRT C/T x 6 Cisplatin 80mg/m2, monthly Cisplatin 100mg/m2, D1Bleomycin 15mg/m2, D3-D7 Cancer 1987; 60: 301-311J Clin Oncol 1990; 8: 838-847

  24. Conclusionof Adjuvant chemotherapy • Poor drug delivery • Decrease distant metastasis • No effect on locoregional control • No survival impact • Owing to insufficient dose density? • Disease nature-related?

  25. Induction chemotherapy

  26. GETTEC, French Cisplatin 100mg/m2, D15-FU 1000mg/m2, D1-D5 q3w, 3 cycles Operable: Surgery  RTInoperable: RT Induction C/T 318, HNSCC, oropharynxstage II-IV Operable: Surgery  RTInoperable: RT British Journal of Cancer 2000; 83: 1594-1598

  27. chemotherapy Overall survivalp=0.03 GETTEC, French No chemotherapy chemotherapy Dz-free survivalp=0.11 No chemotherapy

  28. GSTTC, Italy Cisplatin 100mg/m2, D15-FU 1000mg/m2, D1-D5 q3w, 4 cycles Operable: Surgery  RTInoperable: RT A Induction C/T 237, HNSCC, stage III/IV Operable: Surgery  RTInoperable: RT B Journal of the National Cancer Institute 1994; 86: 265-272 Journal of the National Cancer Institute 2004; 96: 1714-1717

  29. All pts 3-yr distant metastasis rate Overall survival Operable group Inoperable group Overall survival Overall survival

  30. SWOG Cisplatin 50mg/m2, D1MTX 40mg/m2, D1Bleomycin 15U/m2, D1, D8Vincristine 2mg, D1 A Q3w, 3 cycles Surgery  RT 158, Head Neck epidermoid carcinoma, stage III/IV Induction C/T Surgery  RT B  No survival benefit Laryngoscope 1988; 98: 1205

  31. Induction chemotherapy • Good drug delivery • Decrease distant metastasis • GSTTC, SWOG • No improvement of locoregional control • No survival impact • GSTTC: negative impact in surgery group

  32. Concurrent chemoradiotherapy

  33. Sanchiz F et al. Conventional RT 60Gy/30fx, 2Gy/d 859 pts, HNSCCstage III/IV 70.4Gy, 1.1Gy bid HFxRT CCRT (conventional RT) 5FU 250mg/m2, qod Int J Radiat Oncol Biol Phys. 1990; 19: 1347-1350

  34. Browman GP et al CCRT Identical RT in both arms RT: 60Gy/30fx, conventionalC/T: 5-FU 1200mg/m2/d, infusion D1-D3, D22-D24 175 pts, HNSCCT3/T4 RT alone More mucositis, weight loss, and skin toxicity in CCRT arm Journal of Clinical Oncology 1994; 12: 2648-2653

  35. Aldelstein DJ et al RT alone RT: 66-72Gy, conventional, 1.8-2Gy/fx 100 pts, HNSCCstage III/IV Infusion, D1-D4D22-D25 Cisplatin: 20mg/m2/d5FU: 1000mg/m2/d CCRT Residual dz or recurrence Primary site resection +/- neck dissection Survival benefit from better local control Cancer 2000; 88: 876-883

  36. GORTEC CCRT Carbo 70mg/m2/d, D1-D45FU 600mg/m2/d, D1-D4 q3w, 3 cycles 226 pts, oropharynxIII/IV RT alone Identical RT in both arms RT: 7000cGy/35fx, conventional Dose delivery Journal of National Cancer Institute 1999; 91:2081-2086

  37. Jeremic B et al, Japan CCRT (HFxRT) Identical RT in both arms RT: 77Gy/70fx/35d, 1.1Gy bidC/T: 5FU 6mg/m2/d, 5days/wk 130 pts, HNSCCstage III/IV HFxRT alone Similar stomatitis, esophagitis in both arm,more leukopenia and thrombocytopenia in CCRT arm Journal of Clinical Oncology 2000; 18: 1458-1464

  38. ECOG RTOG A: RT alone RT: 7000cGy/35fx, conventionalidentical in three arms 295 pts, HNSCCunresectable III/IV B: CCRT Cisplatin 100mg/m2, D1, D22, D43 CR or unresectable C: CCRT (RT 3000cGy) CCRT (RT 4000cGy) PR Cisplatin 75mg/m2, D15FU 1000mg/m2/d x 4d surgery CCRT (RT 3000cGy) q4w x 3 Journal of Clinical Oncology 2003; 21: 92-98

  39. Taylor SG et al RT 70Gy/35fx Cisplatin 100mg/m2, D15-FU 1000mg/m2, D1-D5 Q3w x 3 C/T  RT (A) 215 pts, HNSCCstage III/IV, unresectable Cisplatin 60mg/m2, D15-FU 800mg/m2, D1-D5 CCRT (B) Qw x 7 NS p=0.011 Journal of Clinical Oncology 1994; 12: 385-395

  40. Concurrentchemoradiotherapy • Enhance locoregional control • Minimal effect in distant metastasis • Improve survival • Superior than sequential chemoradiotherapy • Disease nature: local recurrence predominant • Enhance RT toxicity • Mucositis, skin toxicity, BW loss • Leukopenia depends on C/T type

  41. Cisplatin 100mg/m2, D15FU 640mg/m2/d, CVI, D1-D5Leucovorin 100mg q4h po, D1-D6INF-α 2MU/m2/d, D1-D6 Brockstein B et al PFLI q3w PFLI-FHX 164 pts Induction C/T x 3 CCRT 5FU 800mg/m2/d x 5/wkHydroxyurea 1000mg q12h, 11doses/wkRT 6000cGy/30fx FHX 230 pts Intensified CCRT (C/T)HF2X Cisplatin 100mg/m2, D1 orPaclitaxel 100mg/m2, D1 q3w x 3 5FU 800mg/m2/d x 5/wkHydroxyurea 1000mg q12h, 11doses/wkRT 6000cGy/30fx + J Clin Oncol. 1995; 13: 876-83Annals of Oncology 2004; 15: 1179-1186

  42. Locoregional failure Distant failure Overall survival Progression-free survival J Clin Oncol. 1995; 13: 876-83Annals of Oncology 2004; 15: 1179-1186

  43. Conclusion of CTR before Taxane Era • Induction or adjuvant chemotherapy • Decrease distant metastasis • Related to systemic dose, adequate delivery? • Chemotherapy concurrent with RT • Decrease locoregional recurrence • Enhance RT effect • Add induction chemotherapy to CCRT • To reduce distant failure since local control adequate

  44. Yale 6557 protocol Cisplatin 20mg/m2/d x 4d5FU 800mg/m2/d x 4dLV 500mg/m2/d x 4d CCRT:RT: 70Gy/35fxCisplatin 100mg/m2, q3w q4w C/T: 42 pts, HN cancer, stage III/IVresectable/unresectable C/T x 2 CCRT Non-responder operation • Induction C/T: RR 76% • C/TCCRT: 67% CR Journal of Clinical Oncology 2004; 22: 3061-3069

  45. SWOG Cisplatin 100mg/m25FU 1000mg/m2/d x 5d CCRT:RT: 72Gy/36fxCisplatin 100mg/m2, q3w C/T: q3w 59 pts, HN cancer, resectable stage III/IV C/T x 2 CCRT Non-responder Non-responder operation operation • Induction C/T: RR 78% • C/TCCRT: 54% CR Journal of Clinical Oncology 2005; 23: 88-95

  46. Taxane Era • Improve response rate in metastatic dz • 70% 90% • Incorporate to induction regimen • Eliminate more micrometastasis

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