Presented at KHNOS on May 21 2016, Busan

1. Salvage re-RT for locally recurrent
nasopharynx cancer
Yong Chan Ahn, MD, PhD
Dept. of Radiation Oncology
Samsung Medical Center, Sungkyunkwan University School of Medicine

2. • 2D/3D RT era
• IMRT era
• Review articles
• Surgical viewpoints
• SMC experience
• Proton therapy
• Summary

3. • 2D/3D RT era
• IMRT era
• Review articles
• Surgical viewpoints
• SMC experience
• Proton therapy
• Summary

4. • 176 local recurrence among 903 non-metastatic patients (19.5%) @ PWH
from ’84 till ’89.
• 103 were treated with re-RT, 20 with surgery +/- postop RT, 43 with
palliative Tx.
• Outcomes following high dose re-RT were not satisfactory (OS and LCR
@ 5 years were 7.6% and 15.2%) with TLN in 20.4%.
• DFI ≤1.5 years and advanced rT and rN stages were significantly adverse
prognosticators for OS and/or further LC.
• Restricting to rT1-2, nasopharyngectomy was better than re-RT.
Red 1998

5. 15.2%
7.6%
• In 123 Pts following local
Tx, 5-Yr LCR, RFS, and
OS were 18.7%, 11.5%,
and 9.4%.

7. Unsatisfactory clinical outcomes with
high incidence of severe late toxicity!

8. • 847 local recurrence among 4,460 non-metastatic patients
(19.0%) @ QEH from ’76 till ’85.
• 678 were treated with re-RT.
• Long latency  different behavior.
• Better prognosis d/t lower risk of distant failure.
Red 1999

13. • 319 local recurrence as 1st failure (10.9%) among 2,915 Pts @ HK
Nasopharyngeal Ca Study Group (PWH, TMH, QMH, PYNEH,
and QEH) from ’96 till ’00.
• OS @ 3 years 74%.
• Early initial T and use of salvage Tx were favorable factors.
• Salvage Tx improved OS only in rT1-2, but not in rT3-4.
HN 2005

16. Promising outcomes in early T categories!

17. • 2D/3D RT era
• IMRT era
• Review articles
• Surgical viewpoints
• SMC experience
• Proton therapy
• Summary

18. • Re-RT (IMRT) to 239 locally recurrent NPC Pts @ SYU from ’01 till ’08.
• OS, LCR, DMFS and DFS @ 5 years were 44.9%, 85.8%, 80.6% and
45.4%.
• Pts with rT3-4 and GTV >38 cm3 experienced grade 3-5 late toxicities more
frequently.
• GTV >38 cm3, fractional dose >2.3 Gy, age ≤46 years, rN0 and rI/II stage
were all independent favorable prognostic factors for OS.
Clin Oncol 2012

19. • Re-RT (IMRT) to 151 locally recurrent NPC Pts @ SYU from ’01 till ’06.
• OS, LCR, DMFS and DFS @ 5 years were 38.0%, 80.7%, 83.5% and
69.0%.
• 39% of rIII/IV Pts experienced Grade 3~4 late toxicities.
• Larger rGTV >42 cm3 and rT3-4 were adverse predictors for OS.
EJC 2012

20. • Re-RT (IMRT) to 70 locally recurrent NPC Pts @ Fujian Univ. from ’03 till
’09.
• OS, LCR and DFS @ 2 years were 67.4%, 65.8% and 65.8%.
• Moderate to severe late toxicities in 25 Pts (35.7%): mucosal ulcer (11, 15.7%);
CN palsy (17, 24.3%); trismus (12, 17.1%); and deafness (12, 17.1%).
• Longer DFI ≥36 months and advanced initial T stage were adverse prognostic
factors for OS, LCR and DFS.
Red 2012

21. • 2D/3D RT era
• IMRT era
• Review articles
• Surgical viewpoints
• SMC experience
• Proton therapy
• Summary

22. Oral Oncol 2012
• Tx should be highly individualized, depending on site and extent
of recurrence, availability of equipment and expertise.
• For re-RT, most conformal and precise technique should be
used:
– IMRT and/or FSRT are current standard.
– Hope for proton and particle beam Tx.
– Optimization of dose schedule remains to be explored.

23. Curr Oncol 2013

24. • Surgery for only in very select cases (good patients’ condition;
small rT1-2; technically accessible and resectable)
• Re-RT by 2D/3D RT can lead to very high complication rate
(48%~73% @ 5 years)
• IMRT +/- chemotherapy remains principle modality (OS of
45%~65% @ 5 years)!
CCO 2016

25. • 2D/3D RT era
• IMRT era
• Review articles
• Surgical viewpoints
• SMC experience
• Proton therapy
• Summary

26. • Meta-analysis of 779 patients from 17 studies
• 5-Yr OS, LCR and DMFS of entire cohort were 51.2%,
63.4 %, and 88.7%
Ann Surg Oncol 2014

29. • 894 rNPC patients from ’00 till ’09 @ SYU.
• rT/rN were stratified as resectable and unresectable
and sT/sN were proposed.
EJC 2015

32. sStage I

33. sStage I
sStage II

34. sStage I
sStage II
sStage III

35. • ‘Surgical’ staging system exhibits better prognostic value
for rNPC patient survival and can aid clinicians in
selecting most suitable Tx option.
sStage I
sStage II
sStage III

36. • 2D/3D RT era
• IMRT era
• Review articles
• Surgical viewpoints
• SMC experience
• Proton therapy
• Summary

37. SMC Experience
• 72 Pts with local or regional recurrence
underwent salvage re-RT from ’95 to ’15
@ SMC
• Median DFI between initial RT and re-RT
= 22.8 (3.4~111.0) months
• 54 local +/- neck; 18 regional only
• Symptoms @ recurrence:
– cranial neuropathy (n=8), local pain
(n=5), obstructive Sx (n=2), and
bleeding (n=2)
Characteristics Number
Median age (range) 50 (28-73) years
Sex
M 52 (72.2%)
F 20 (27.8%)
ECOG PS
0-1 54 (75.0%)
2-3 18 (25.0%)
Histologic type
Squamous cell ca. 17 (23.6%)
Non-keratinizing ca. 12 (16.7%)
Undifferentiated ca. 40 (55.6%)
Carcinoma, NOS 3 (4.2%)
Sx at recurrence
Yes 55 (76.4%)
No 17 (23.6%)
rT (AJCC 7th)
0 18 (25.0%)
1-2 22 (30.6%)
3-4 32 (44.4%)
rN (AJCC 7th)
0 41 (56.9%)
1 26 (36.1%)
2 4 (5.6%)
3 1 (1.4%)
Number of recurrence
Single 55 (76.4%)
Multiple 17 (23.6%)

40. • 2D/3D RT era
• IMRT era
• Review articles
• Surgical viewpoints
• SMC experience
• Proton therapy
• Summary

41. • 16 recurrent HNC treated with particle beams @
Heidelberg.
Green 2011

42. • Treatment was tolerated well without severe acute toxicity.
• Favorable overall response rate @ 8 weeks (53.3%) in non-chordoma/
chondrosarcoma Pts; stable disease in 4/5 chordoma/chondrosarcoma Pts.
• Scanned particle beams in recurrent HNC seems feasible and
encouraging.

43. • Comparative dose planning with robust IMPT vs HT in 7
recurrent HNC patients @ Univ. Duisburg-Essen.
Rad Oncol 2013

44. • HT yielded steeper dose gradients @ ≤7.5 mm outside target and more
conformal high dose regions than IMPT.
• Comparable robustness against set-up errors of up to 2 mm by both.
• Satisfactory normal tissue exposure by both.
• IMPT delivered smaller mean body dose.
• Comparative dose planning is recommended!

45. • Comparison of IMPT and IMRT by 1:2 matching @ MDACC
from ’11 till ’13.
Int J Particle Ther 2015

47. • Significantly lower mean doses to
OC, brainstem, whole brain, and
mandible by IMPT.

48. • Less GT insertion mainly by lower OC dose by IMPT (2 vs 13).

49. • There appears to be significant clinical benefit for protons
in full dose re-RT of skull-base tumors, although additional
F/U is required.
• Integration of IMPT is still considered investigational for
bulky OPSCC and requires strict attention to variables
causing dose deposition uncertainty.
• Results of ongoing randomized trial (IMPT vs IMRT for
OPSCC) will provide valuable insight into safety and
potential for reduced toxicity with IMPT.
Curr Opin 2015

50. • Pending additional clinical and health economic evidence,
allocation of patients to IMPT vs IMRT is done on case-by-
case basis, weighing expected costs and benefits.
• Biological optimization, taking advantage of biological
effectiveness, holds potential to further enhance therapeutic
ratio with proton therapy.
Curr Opin 2015

51. Soon or later, more and more will come!

52. • 2D/3D RT era
• IMRT era
• Review articles
• Surgical viewpoints
• SMC experience
• Proton therapy
• Summary

54. Therapeutic Ratio
% tumor control by therapy A vs therapy B
Therapeutic Gain Factor (TGF) =
% complications by therapy A vs therapy B

55. Proton Therapy Center
Samsung Medical Center