Radiotherapy in nasopharynx

Role of radiotherapy in the management of nasopharynx, 2D, IMRT and literature review

1. Radiotherapy in Nasopharynx Dr Pallavi Kalbande

2. Indications for RT

3. Why Radiotherapy?

4. Basic principles of RT Primary plus whole neck need to be treated 70 Gy or equivalent dose – Primary plus involved nodes 60 Gy – High risk of involvement 50 - 5 4 P r o p h y l a c t i c d o s e Total dose is the main determining factor in out come Increased dose per fraction – long term toxixity T1-T2- 5 yr LC- 90-100% T 3 - T 4 – 40 - 70 % w i t h 7 G y

5. Positioning and immobilization supine with head and shoulders immobilised with 5 clamp thermoplastic mask chin is elevated to spare the oral cavity and orbit spine should be kept as straight as possible if posterior neck nodes are present, to facilitate matching of an electron boost A mouth bite may be used to depress the tongue If IMRT is used, the patient can be immobilised with the chin in a neutral position

6. Ho’s Technique

7. Anatomical Landmarks

8. Inferior border at the anterior commissure of lip

9. 2D to IMRT

10. 3DCRT and IMRT CT scan slices measuring 3–5 mm are obtained From 2 cm above the superior orbital ridge (to include the skull base) to the arch of the aorta inferiorly Intravenous contrast Reference marks are placed on the shell at the CT visit to aid verification

11. GTV primary and nodes

12. High risk CTV_HR (CTV_70)

13. Intermediate risk CTV_IR (CTV_63) CTV_HR + 5mm

14. RT prescription

15. Conventional Vs IMRT

16. 5yr Efficacy results

17. Acute complications

18. Late complications

19. Addition of chemotherapy

20. Intergroup Trial N=193 Concurrent Chemo RT 70 Gy/ 35# + 3 cycles of CDDP RT alone Adjuvant Chemotherapy (CDDP + 5 FU) x 3 Al sarraf et al JCO 98 16:

21. U.S. Intergroup 0099 3Y PFS 69% (CRT) vs . 24% (RT alone), p <0.001 45% 3yrs PFS 3Y OS 76% (CRT) vs . 46% (RT alone), p =0.005 30% 3 yrs OS benefit Al sarraf et al JCO 98 16: 1310-7

22. U.S. Intergroup 0099 Issues Flawed study design Are the benefits from chemo due to concurrent administration, adjuvant, or both? Terminated early after interim analysis showed survival benefit RT alone arm performed worse than expected Old RT techniques Many patients enrolled had WHO type I NPC (not EBV- associated) Adjuvant PF chemotherapy only feasible in some patients

23. Subsequent Asian Trials Contradictory 3Y OS Rate of DM Wee, JCO, 2005 (Singapore) 221 pts WHO type II/II M o s t l y T 3 -4 + / o r N2-3 Cis/RT ➟ PF X3 80% 18% RT alone 65% 38% p = . 006 1 p = . 002 9 Lee, JCO, 2005 (Hong Kong) 348 pts WHO type II/II Mostly N2-3 Cis/RT ➟ PF X3 78% 24% RT alone 78% 27% p = . 9 7 p = . 9 6 J C li n O n c o l 23 : 6730 - 6738 . J C li n O n c o l 23 : 6966 - 6975 .

24. P=.004 NS NS J Clin Oncol 22:4604-4612. © 2004 by American Society of

25. HR for death=0.82 (95% CI 0.71-0.95) 6% absolute survival benefit at 5 yrs Greatest benefit from concurrent chemo HR=0.60 (concurrent) HR=0.97 (adjuvant) Int. J. Radiation Oncology Biol. Phys., Vol. 64, No. 1, pp. Meta-analysis in MAC-NP C- Collaborative Group

26. The aim of this study was to update the meta-analysis, include recent trials, and to analyse separately the benefit of concomitant plus  adjuvant chemotherapy 19 trials and 4806 patients Median follow-up was 7·7 years 

27. Results A ddition of chemotherapy to radiotherapy significantly improved overall survival absolute benefit at 5 years 6·3%. PFS, LRC was also better   Concomitant plus adjuvant chemotherapy had maximum benefit then concomitant without adjuvant chemotherapy but not adjuvant chemotherapy alone or  induction chemotherapy  alone

28. Network Meta-analysis All randomized trials of radiotherapy (RT) with or without chemotherapy in nonmetastatic nasopharyngeal carcinoma were considered 20 trials and 5,144 patients were included Treatments were grouped into seven categories: RT alone (RT) IC followed by RT (IC-RT) RT followed by AC (RTAC) IC followed by RT followed by AC (IC-RT-AC) concomitant chemoradiotherapy (CRT) IC followed by CRT (IC-CRT) CRT followed by AC (CRT-AC)

29. Conclusion Results The three treatments with the highest probability of benefit on overall survival (OS) were CRT-AC CRT IC-CRT

30. IMPT first nine patients treated with IMPT for NPC With a median follow-up of just over 2 years no patients developed local or regional recurrence one patient developed distant metastatic disease and subsequently died. 

31. Altered fractionation

32. Study design 189 eligible patients were randomized to one of four treatment groups CF CF + C AF AF + C Concurrent-adjuvant chemotherapy combined with AF significantly reduced failure and cancer-specific deaths major late toxicity and incidental deaths were statistically insignificant