ESTRO 2026, Stockholm, İsveç, 15 - 19 Mayıs 2026, ss.5652-5653, (Özet Bildiri)
Prognostic Impact of Pretreatment EBV-DNA CopyNumber per Unit Tumor Volume in Patients withNasopharyngeal Carcinoma – A Retrospective Single-Center Study
Mehmet Varol
Faruk Recep Özalp
Ece Özkaya
Halit Can Koç
Hasan Oğuz Çetinayak
Abstract
Background: To evaluate a simple pre-treatment log indexcombining circulating Epstein–Barr Virus DNA (EBVDNA) with total gross tumor volume (GTVt) for prognostication in nasopharyngeal carcinoma (NPC): EBVDNA-Volume Index (EVI) = Ln[(EBVDNA+1) × (GTVt+2)].
Methods: In a single-center retrospective cohort, 70consecutive patients diagnosed with stage II–III NPC whoreceived definitive radiotherapy (RT) combined withinduction, concurrent, or adjuvant chemotherapy (CT) between 2014 and 2025 were evaluated.
All patients were older than 18 years and had pretreatmentplasma EBV-DNA levels measured prior to any therapy. Forpatients who received induction CT, pre-treatment magneticresonance imaging (MRI) of the neck/nasopharynx or positronemission tomography/computed tomography (PET/CT) scansobtained before the first chemotherapy cycle were fused withplanning CT simulation (CT-sim) images. For patients whodid not receive induction CT, MRI or PET/CT scansperformed prior to RT+CT were used for image fusion. Theprimary tumor and retropharyngeal lymph node (GTVp) together with the involved cervical lymph nodes (GTVn) werecontoured as GTVt.
The primary endpoint was overall survival (OS); disease-freesurvival (DFS) was secondary. Associations were tested withuni- and multivariable Cox regression. Discrimination wasassessed with Harrell’s c-index. An optimal cut-off of 13.3 forEVI was derived by ROC-curve analysis (Youden’s J). Kaplan–Meier estimates were compared with log-rank testsusing SPSS v26.
Results: Median follow-up time was 55.50 (1-122) months. During follow-up, 19 OS and 27 DFS events occurred. Seven-year OS and DFS were 74.6% and 67.9%, respectively. Per standard-deviation (SD) increase, EBVDNA predicted OS (univariable HR 2.51, 95% CI 1.02–6.20; multivariableHR 2.36, 95% CI 1.14–4.94; p=0.021) and GTVt predictedOS (univariable HR 1.36, 95% CI 1.02–1.81; multivariableHR 1.37, 95% CI 1.02–1.85; p=0.038). EVI showed c-index0.723 (95% CI 0.585–0.860), exceeding TNM stage (c-index0.674, 95% CI 0.544–0.804). By the ROC-derived cutoff, median OS was 98 months (95% CI 87-106) for EVI<13.3 vs 81 months (95%CI 70-91) for ≥13.3 (p=0.002). Higher EVIvalues correlated with higher EBVDNA levels.
Conclusion: The pre-treatment EVI is an independentpredictor of OS in stage II-III NPC patients and mayoutperform TNM staging for risk discrimination. Because it relies on readily available inputs, it could support risk-adaptedmanagement; external, multi-center validation is warranted.
Keywords: nasopharyngeal carcinoma; EBV DNA; GTV; prognostic index
Table 1. Patient Characteristics
| All cohort n=70, % | Index<13.3 n=49, % | Index≥13.3 n=21, % |
Age, n (%) <50 ≥50 |
36 (50.1) 34 (50.9) |
26 (53.1) 23 (46.9) |
10 (47.6) 11 (52.4) |
Sex, n (%) Male Female |
52 (74.3) 18 (25.7) |
35 (71.4) 14 (28.6) |
17 (81.0) 4 (19.0 |
ECOG PS, n (%) 0 ≥1 |
61 (87.1) 9 (12.9) |
46 (93.9) 3 (6.1) |
15 (87.1) 6 (28.9) |
CCI 0-2 ≥3 |
33 (47.1) 37 (52.9) |
25 (51.0) 24 (49.0) |
8 (38.1) 13 (61.9) |
TNM stage, n (%) 2 3 |
36 (51.4) 34 (48.6) |
31 (63.3) 18 (36.7) |
5 (23.8) 16 (76.2) |
T category, n (%) 1 2 3 4 |
19 (27.1) 24 (34.3) 11 (15.7) 16 (22.9) |
15 (30.6) 18 (36.7) 8 (16.3) 8 (16.3) |
4 (27.1) 6 (34.3) 3 (15.7) 8 (22.9) |
N category, n (%) 0-1 2 3 |
17 (24.3) 32 (45.7) 21 (30.0) |
15 (30.6) 24 (49.0) 10 (20.4) |
2 (9.5) 8 (38.1) 11 (52.4) |
EBVDNA <2000 ≥2000 |
44 (50.0) 26 (50.0) |
43 (87.8) 6 (12.2) |
1 (4.8) 20 (95.2) |
GTVp volume, cc (IQR) | 36 | 35 | 38 |
GTVn volume, cc (IQR) | 31 | 20 | 59 |
GTVt volume, cc (IQR) | 67 | 55 | 95 |
First line treatment, n (%) CCRT RT monotherapy IC+CCRT |
43 (61.4) 6 (8.6) 21 (30.0) |
30 (61.2) 5 (10.2) 14 (28.6) |
13 (61.9) 1 (4.8) 7 (33.3) |
Abbrevations: ECOG PS: Eastern Cooperative Oncology Group Performance Status, CCI: Charlsoncomorbidity index, EBVDNA: epstein-barr virüs DNA, GTVp: primary tumor and retropharyngeal lymph nodegross tumor volume, GTVn: cervical lymph nodes gross tumor volüme, GTVt: total gross tumor volüme, CCRT: concurrent chemoradiotherapy, IC: induction chemotherapy
Median OS time
EVI<13.3: 98 months (95% CI 87-106)
EVI ≥13.3: 81 months (95%CI 70-91)
p=0.002
Fig.1. Overall Survival Curves of groups according to EVI; blue line EVI<13.3 patients, red line EVI>13.3.
Table 2. Univariate and multivariate analysis for OS
| Univariate analysis HR(95%CI) p- value* | Multivariate analysis HR(95%CI) p- value* | ||
Age (<50 vs ≥50) | 3.31 (0.89-12.3) | 0.074 |
|
|
Sex (Female vs Male) |
| 0.175 |
|
|
ECOG P (0 vs ≥1) | 2.01 (0.54-7.5) | 0.295 |
|
|
T category (1-2 vs 3-4) | 3.22 (0.96-10.8) | 0.057 |
|
|
EBVDNA copy (1 per SD) | 2.51 (1.02-6.2) | 0.044 | 2.36 (1.14-4.94) | 0.021 |
GTVp (1 per SD) | 1.23 (0.99-1.58) | 0.102 |
|
|
GTVn (1 per SD) | 1.38 (0.84-2.27) | 0.204
|
|
|
GTVt (1 per SD) | 1.36 (1.02-1.81) | 0.036 | 1.37 (1.02-1.85) | 0.038 |
CCRT vs CCRT+ IC | 1.28 (0.33-4.87) | 0.719
|
|
|
*p <0.05. Abbrevations: ECOG PS: Eastern Cooperative Oncology Group Performance Status, tumorvolume, GTVn: cervical lymph nodes gross tumor volüme, GTVt: total gross tumor volüme, CCRT: concurrentchemoradiotherapy, IC: induction chemotherapy