Prognostic value of plasma EBV DNA for nasopharyngeal cancer patients during treatment with intensity-modulated radiation therapy and concurrent chemotherapy

Chawalit Lertbutsayanukul; Danita Kannarunimit; Anussara Prayongrat; Chakkapong Chakkabat; Sarin Kitpanit; Pokrath Hansasuta

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Prognostic value of plasma EBV DNA for nasopharyngeal cancer patients during treatment with intensity-modulated radiation therapy and concurrent chemotherapy

Chawalit Lertbutsayanukul

| 28 avr. 2018

Radiology and Oncology

Édition 52 (2018): Edition 2 (June 2018)

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Article Category: Research Article

Publié en ligne: 28 avr. 2018

Pages: 195 - 203

Reçu: 21 déc. 2017

Accepté: 04 févr. 2018

DOI: https://doi.org/10.2478/raon-2018-0016

© 2018 Chawalit Lertbutsayanukul, Danita Kannarunimit, Anussara Prayongrat, Chakkapong Chakkabat, Sarin Kitpanit, Pokrath Hansasuta, published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Kaplan -Meier curves for the overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) stratified by stage and plasma EBV DNA at different time points.

Kaplan-Meier curves for the overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) stratified by a combination of stage and mid-EBV concentration.

Univariate analyses for the clinical parameters and EBV values associated with the overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS

	Hazard ratio for OS	Univariate			Hazard ratio for PFS	Univariate			Hazard ratio for DMFS	Univariate

		95.0% CI		p-value		95.0% CI		p-value		95.0% CI		p-value

		Lower	Upper			Lower	Upper			Lower	Upper
Age <45 vs. ≥45	0.497	0.185	1.331	0.164	0.655	0.319	1.346	0.250	0.807	0.353	1.845	0.611
Sex Male vs. Female	1.442	0.493	4.222	0.504	1.623	0.679	3.879	0.276	1.078	0.434	2.677	0.872
WHO type IIA vs. IIB	1.344	0.399	4.532	0.633	1.795	0.748	4.31	0.190	2.101	0.719	6.141	0.175
T Stage				0.152				0.026				0.119
T1 vs. T4	0.155	0.031	0.773	0.023	0.176	0.055	0.564	0.003	0.212	0.05	0.89	0.034
T2 vs. T4	0.73	0.257	2.073	0.555	0.523	0.224	1.222	0.134	0.617	0.204	1.862	0.391
T3 vs. T4	0.667	0.223	1.991	0.468	0.73	0.319	1.671	0.457	0.93	0.316	2.743	0.896
N Stage				0.740				0.501				0.188
N1 vs. N3	1.222	0.386	3.865	0.733	0.887	0.368	2.138	0.789	0.587	0.208	1.657	0.314
N2 vs. N3	0.844	0.297	2.4	0.750	0.651	0.302	1.406	0.275	0.445	0.187	1.063	0.068
Stage				0.253				0.070				0.102
Stage II vs. IVa-b	0.888	0.281	2.8	0.839	0.491	0.166	1.449	0.198	0.326	0.073	1.451	0.141
Stage III vs. IVa-b	0.484	0.2	1.17	0.107	0.472	0.242	0.92	0.028	0.47	0.214	1.034	0.061
Tech SIB vs. SEQ	1.619	0.707	3.71	0.255	1.309	0.693	2.472	0.407	1.461	0.674	3.167	0.336
Concurrent chemotherapy 0-5 vs. 6-7 cycles	1.172	0.525	2.616	0.699	0.795	0.418	1.514	0.486	0.632	0.287	1.393	0.255
Adjuvant chemotherapy 0-2 vs. 3 cycles	1.089	0.432	2.748	0.856	1.101	0.536	2.263	0.793	0.937	0.377	2.327	0.888
Pre-EBV ≥ 2010 vs. < 2010	1.760	0.524	5.915	0.360	2.309	0.819	6.512	0.114	1.595	0.550	4.625	0.390
Mid-EBV detectable vs undetectable	2.600	1.031	6.556	0.043	2.746	1.337	5.640	0.006	2.041	0.772	5.397	0.15
Post-EBV detectable vs. undetectale	5.923	1.989	17.638	0.001	5.961	2.457	14.465	<0.001	29.758	8.155	108.593	<0.001

Overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), local progression-free survival (LPFS) and regional progression-free survival (RPFS) rates among different plasma EBV time points

	3-year OS(95%CI)	p-value	3-year PFS(95%CI)	p-value	3-year DMFS(95%CI)	p-value	3-year LPFS(95%CI)	p-value	3-year RPFS(95%CI)	p-value
Pre-EBV < 2010	88.4 (73.1–103.7)	0.360	82.9 (65.3–100.5)	0.114	82.9 (62.3–100.5)	0.386	100	0.328	100	0.475
Pre-EBV ≥ 2010	82.1 (73.9–30.3)	0.360	76.2 (67.0–85.4)	0.114	85.2 (77.0–93.4)	0.386	94.4 (89.1–99.6)	0.328	96.6 (91.9–101.3)	0.475
Undetectable mid-EBV	86.0 (78.5–93.4)	0.040	81.5 (73.3–89.7)	0.006	86.1 (78.5–93.7)	0.15	97.5 (94.0–101.0)	0.01	98.6 (95.9–101.3)	0.113
Detectable mid-EBV	66.7 (42.8–90.6)	0.040	52.5 (26.8–78.2)	0.006	76.6 (52.9–100.3)	0.15	79.5 (53.8–105.2)	0.01	87.5 (64.6–110.4)	0.113
Undetectable post-EBV	86.1 (79.0–93.2)	< 0.001	79.9 (71.9–87.9)	< 0.001	88.2 (81.3–95.1)	< 0.001	97.6 (94.3–100.9)	< 0.001	97.2 (93.5–100.9)	0.841
Detectable post-EBV	42.9 (6.3–79.6)	< 0.001	42.9 (6.3–79.6)	< 0.001	22.9 (15.7–61.5)	< 0.001	33.3 (20.0–86.6)	< 0.001	100	0.841

Patient characteristics

	N = 105
Age < 45	34 (32.4%)
Age ≥ 45	71 (67.6%)
Sex
Male	82 (78.1%)
Female	23 (21.9%)
T-stage
1	30 (28.6%)
2	28 (26.7%)
3	29 (27.6%)
4	18 (17.1%)
N-stage
0	1 (1.0%)
1	26 (24.8%)
2	57 (54.3%)
3	21 (20.0%)
Stage grouping (AJCC 2010)
II	14 (13.3%)
III	54 (51.4%)
IVa-b	37 (35.2%)
WHO subtypes
2A	11 (10.5%)
2B	94 (89.5%)
Mid-EBV
undetectable	90 (85.7%)
detectable	15 (14.3%)
Post-EBV
undetectable	98 (93.3%)
detectable	7 (6.7%)

Multivariate analyses for the clinical parameters and EBV values associated with the overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS)

	Hazard ratio for OS	95.0% CI for OS		P-value

		Lower	Upper
Age < 45 vs. ≥ 45	0.409	0.140	1.190	0.101
T				0.305
T1 vs. T4	0.286	0.052	1.570	0.150
T2 vs. T4	1.214	0.361	4.078	0.754
T3 vs. T4	1.177	0.341	4.069	0.796
Mid-EBV undetectable vs detectable	1.620	0.617	4.251	0.327
Post-EBV undetectable vs. detectable	6.881	1.699	27.867	0.007

	Hazard ratio for PFS	95.0% CI for PFS

		Lower	Upper

Age <45 vs. ≥ 45	0.422	0.180	0.988	0.047
WHO type IIA vs. IIB	1.354	0.441	4.159	0.597
T Stage				0.101
T1 vs. T4	0.497	0.104	2.375	0.381
T2 vs. T4	1.660	0.450	6.125	0.446
T3 vs. T4	2.099	0.646	6.825	0.218
Stage				0.099
Stage II vs. IVa-b	1.016	0.256	4.035	0.982
Stage III vs. IVa-b	0.416	0.170	1.021	0.055
EBV < 2010 vs. ≥ 2010	0.370	0.113	1.211	0.100
Mid-EBV undetectable vs. detectable	1.427	0.630	3.234	0.394
Post-EBV undetectable vs. detectable	5.117	1.562	16.768	0.007

	Hazard ratio for DMFS	95.0% CI for DMFS

		Lower	Upper

WHO type IIA vs. IIB	1.653	0.470	5.810	0.433
T Stage				0.113
T1 vs. T4	0.945	0.068	13.158	0.966
T2 vs. T4	5.632	0.388	81.647	0.205
T3 vs. T4	4.628	0.384	55.737	0.228
N Stage				0.410
N1 vs. N3	4.484	0.305	65.955	0.274
N2 vs. N3	2.018	0.151	26.935	0.595
Stage				0.340
Stage II vs. IVa-b	0.090	0.003	2.435	0.153
Stage III vs. IVa-b	0.150	0.009	2.474	0.185
Mid-EBV undetectable vs detectable	1.583	0.517	4.843	0.421
Post-EBV undetectable vs. detectable	129.071	19.031	875.364	0.000

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Prognostic value of plasma EBV DNA for nasopharyngeal cancer patients during treatment with intensity-modulated radiation therapy and concurrent chemotherapy

Article Category: Research Article

Publié en ligne: 28 avr. 2018

Pages: 195 - 203

Reçu: 21 déc. 2017

Accepté: 04 févr. 2018

DOI: https://doi.org/10.2478/raon-2018-0016

© 2018 Chawalit Lertbutsayanukul, Danita Kannarunimit, Anussara Prayongrat, Chakkapong Chakkabat, Sarin Kitpanit, Pokrath Hansasuta, published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Figure 1

Figure 2

Univariate analyses for the clinical parameters and EBV values associated with the overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS

Overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), local progression-free survival (LPFS) and regional progression-free survival (RPFS) rates among different plasma EBV time points

Patient characteristics

Multivariate analyses for the clinical parameters and EBV values associated with the overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS)