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

• 2D/3D RT era

• IMRT era

• Review articles

• Surgical viewpoints

• SMC experience

• Proton therapy

• Summary

• 2D/3D RT era

• IMRT era

• Review articles

• Surgical viewpoints

• SMC experience

• Proton therapy

• Summary

• 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

15.2%

7.6%

• In 123 Pts following local

Tx, 5-Yr LCR, RFS, and

OS were 18.7%, 11.5%,

and 9.4%.

Unsatisfactory clinical outcomes with

high incidence of severe late toxicity!

• 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

• 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

Promising outcomes in early T categories!

• 2D/3D RT era

• IMRT era

• Review articles

• Surgical viewpoints

• SMC experience

• Proton therapy

• Summary

• 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

• 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

• 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

• 2D/3D RT era

• IMRT era

• Review articles

• Surgical viewpoints

• SMC experience

• Proton therapy

• Summary

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.

Curr Oncol 2013

• 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

• 2D/3D RT era

• IMRT era

• Review articles

• Surgical viewpoints

• SMC experience

• Proton therapy

• Summary

• 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

• 894 rNPC patients from ’00 till ’09 @ SYU.

• rT/rN were stratified as resectable and unresectable

and sT/sN were proposed.

EJC 2015

sStage I

sStage I

sStage II

sStage I

sStage II

sStage III

• ‘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

• 2D/3D RT era

• IMRT era

• Review articles

• Surgical viewpoints

• SMC experience

• Proton therapy

• Summary

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%)

• 2D/3D RT era

• IMRT era

• Review articles

• Surgical viewpoints

• SMC experience

• Proton therapy

• Summary

• 16 recurrent HNC treated with particle beams @

Heidelberg.

Green 2011

• 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.

• Comparative dose planning with robust IMPT vs HT in 7

recurrent HNC patients @ Univ. Duisburg-Essen.

Rad Oncol 2013

• 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!

• Comparison of IMPT and IMRT by 1:2 matching @ MDACC

from ’11 till ’13.

Int J Particle Ther 2015

• Significantly lower mean doses to

OC, brainstem, whole brain, and

mandible by IMPT.

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

• 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

• 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

Soon or later, more and more will come!

• 2D/3D RT era

• IMRT era

• Review articles

• Surgical viewpoints

• SMC experience

• Proton therapy

• Summary

Therapeutic Ratio

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

Proton Therapy Center

Samsung Medical Center