NPC Treatment Outcomes: Disease Control and Failure Patterns Sandeep Samant, MS, FRCS

Lee, 1992 n = 5037 ( ) I,II,III,IV: 9,13, 50,22% 2DRT, 65Gy. No RT to neck (70%) OS 50% Lee, 2005 N = 2687 ( ) I,II,III,IV: 7,41,25,28% 2DRT (10% 3D) 66y + boost in 55%. Chemo 23% OS 75% “There has been a substantial improvement in the outcome of treatment in the last 2 decades.”  Improved imaging: MR  Improved radiation: Boost, conformal therapy, neck radiation  Improvements in salvage surgery  Addition of chemotherapy

 Intergroup 0099, 1998: First RCT to show a clear benefit of adding chemotherapy.  CRT (conc-adj) vs. RT for stage III, IV  3yr PFS: 24% vs 69%; 3yr OS: 78% vs 47%  Criticisms:  Poor outcome in RT group  Case mix (25% WHO type 1)  Early closure  Since then, 15 RCT and 2 meta-analyses have been published.

 MAC-NPC, Baujat et al, 2006  8 trials, 1753 patients, fu 6yrs  OS: HR 0.82 (6% benefit at 5yrs - 62 vs 55%)  EFS: HR 0.76 (10% benefit at 5yrs)  Failure pattern:  LRF 46%, DM 38%  Chemo improved both local (HR 0.76) and distant (HR 0.72) control  Only concurrent chemo accorded any benefit (HR 0.6)  No survival benefit with induction or concurrent chemotherapy

 MAC-NPC, Baujat et al, 2006  Chemotherapy was much more effective for type 1 tumors compared to types 2 or 3 (p=.003)  However, the benefit of chemotherapy remained even when type 1 tumors were removed from analysis. “There is level 1 evidence to support the use of chemotherapy in addition to radiation for advanced NPC. The benefit is modest” “The benefit of chemotherapy is only seen when this is administered concurrently. There is no good evidence to support the use induction or adjuvant chemotherapy.”

“Although chemotherapy is more effective for WHO type 1 tumors, its benefit is significant even with the type 2,3 tumors.” “Chemotherapy reduces the likelihood of failure both locally as well as distantly.” “Despite the use of chemotherapy, the risk of distant failure still persists.”

 Neo(MEPFL) - conc vs conc for Stage IVA/B NPC  Adjuvant chemo in EBV-residual (high-risk) NPC  Neo-conc vs Conc-adj with conventional vs accelerated RT  Geftinib + celecoxib for NPC  EBV specific CTL following anti-CD45 MAB EBV-specific immunotherapy for NPC  EBV-specific immunotherapy for NPC Ongoing trials in NPC