1. 高雄榮民總醫院耳鼻喉頭頸部 林陞樵 林曜祥 康柏皇 張庭碩
The Impact of Cumulative Cisplatin Dose on Outcomes of N3 Nasopharyngeal Carcinoma Patients in the Era of IMRT
高雄榮民總醫院耳鼻喉頭頸部
林陞樵 林曜祥 康柏皇 張庭碩

2. Introduction

3. Treatment Effect of Nasopharyngeal Carcinoma (NPC)
Radiotherapy (RT) with chemotherapy (CT)
Better
Survival advantage
Locoregional control
Distant control
Acute toxicity
Dyspepsia
Nephrotoxicity
Neutropenia
Late toxicity
Xerostomia
Hearing impairment
Subcutaneous fibrosis
Balanced cumulative dose? Beneficial group?
Al-Sarraf, M., et al. (1998). J Clin Oncol 16(4):
Lee, A. W., et al. (2011). Eur J Cancer 47(5):
Wang, J., et al. (2015). Transl Oncol 8(6):
Zeng, L., et al. (2014). Br J Cancer 110(1):

4. Cumulative Cisplatin Dose (CCD)
Head and Neck SCC
NPC
CCD ≥ 200mg/m2 in concurrent CT
 Better survival
CCD ≥ 200mg/m2 ?
CCD ≥ 240mg/m2 ?
CCD ≥ 300mg/m2 ?
No difference?
 Still controversial in NPC!!!
Heterogeneous RT modalities without focused group.
Al-Mamgani, A., et al. (2017). Eur Arch Otorhinolaryngol 274(10):
Ou, X., et al. (2017). J Cancer 8(14):
Peng, H., et al. (2016). Sci Rep 6:

5. Materials and Methods

6. Inclusion and Exclusion Criteria
161 patients
NPC undergoing primary IMRT with concurrent CT and/or adjuvant chemotherapy (AC)
From February 2006 to September 2015
Exclusion
Prior RT or CT
Aborting the RT
Without complete dosage records of CT
With concurrent or adjuvant regimens injected other than cisplatin

7. Parameter and Outcome Distant-metastasis free survival (DMFS)
Disease-specific survival (DSS)
Overall survival (OS)
CCD during CCRT
Clinical T and N staging according to AJCC 7th edition

8. Results

9. Table 1 Patient characteristics
Treatment Modalities
Variable
All
Cisplatin dose <200
Cisplatin dose ≧200 P
Age
49.21±10.98
49.64±9.76
0.794
Male gender (%)
116(72.0)
56(65.1)
60(80.0)
0.036
Smoking (%)
 52(32.3)
 23(26.7)
29(38.7) 
0.107
CCIS (%) ≧1
30(18.6)
16(18.6)
14(18.7)
0.992
NUC type
143(88.8)
74(86.0)
69(92.0)
0.232
T stage (%)
0.527 T1
43(26.7)
24(27.9)
19(25.3) T2
21(13.0)
10(11.6)
11(14.7) T3
67(41.6)
39(45.3)
28(37.3) T4
13(15.1)
17(22.7)
N stage (%)
0.032 N0
8(5.0)
5(5.8)
3(4.0) N1
19(11.8)
11(12.8)
8(10.7) N2
113(70.2)
65(75.6)
48(64.0) N3
16(21.3)
Stage 4 (%)
48(29.8)
19(22.1)
29(38.7)
0.022
Adjuvant CT
54(33.5) 
 21(24.4)
 33(44.0)
0.009
RT duration
7.10±0.77
7.07±0.84
0.765
Hemoglobin
13.95±1.83
14.09±1.31
0.570

10. Table 2　Univariate analyses of risk factors for 3-year LRFS, DMFS, DSS, and OS rates
Variable
DMFS (%) p
DSS (%)
OS (%)
Age (y) <50
 92.2
0.428
0.098
 87.7
0.151
Male gender
93.5
0.036
89.6
0.213
83.4
0.917
Smoking
91.7
0.662
87.4
0.913
83.9
0.940
CCIS ≧1
96.2
0.229
92.1
0.358
89.7
0.389
T3/4
94.5
0.035
0.249
84.7
0.659 N3
63.2
<0.001
0.006
AJCC Stage 4
 79.6
0.004
74.9
0.002
72.0
0.018
CCD ≧200
91.3
0.639
85.7
0.590
81.4
0.557
Adjuvant CT
0.560
89.9
0.461
85.9
0.506

11. Table 3　Multivariate analysis for 3-year DMFS, DSS and OS for all patients
DMFS
DSS OS
Variable
Comparison p
HR (95% CI)
Sex
Female vs. Male
0.043
2.898 ( )
T stage
T3/T4 vs. T1/T2
0.080
0.385 ( )
N stage
N3 vs. N0/N1/N2
<0.001
( )
0.001
4.78 ( )
0.009
3.195 ( )
CCD
≧200 vs. <200
Adjuvant CT
Yes vs. No
0.067
0.285 ( )

12. Table 4　Univariate analyses of concurrent cisplatin dose on N3 patients (n=21) for 3-year LRFS, DMFS, DSS, and OS rates
Variable
DMFS (%)
p (one-tailed)
DSS (%)
OS (%)
CCD
0.101
0.06
<200
40.0
≧200
71.4
CCD<200 n=5; CCD>=200 n=16
柱狀圖

13. Discussion

14. Advantaged Cut-off Value of CCD
Total group
CCD ≥ 200mg/m2 NOT beneficial
N3 group
CCD ≥ 200mg/m2 MIGHT BE beneficial
Low case number

15. Potential Survival Benefit in N3 group
CCD ≥ 200 mg/m2  Lower OS, DSS, and DMFS in N3 group
Corelated results with previous studies
IC + CCRT in advanced NPC  better OS, DSS, and DMFS
CCRT + AC in advanced NPC  better OS, PFS, LRFS
IC: stage T1-4/N2-3/ M0
AC: stage III–IVB (except T3-4N0)
Sun, Y., et al. (2016). Lancet Oncol 17(11):
Lee, A. W. M., et al. (2017). Cancer 123(21):

16. Effect of IMRT Heterogeneous RT modalities in previous studies
IMRT  better survival than 2D-RT
IMRT with concurrent CT  reduced DMFS
Peng  LRFS
Zhang, B., et al. (2015). Oral Oncol 51(11):
Peng, G., et al. (2012). Radiother Oncol 104(3):

17. Conclusion N3 status Lower OS, DSS, and DMFS
CCD ≥ 200 mg/m2  Survival benefit?
NO statistical significance in total group
BETTER survival outcomes in patients staged N3
Higher CCD
May be exclusively applied on N3 disease
Avoid rigorous toxicity
Conclusion

18. Thank you for your attention !