Edited by: Giuseppe Maria Milano, Bambino Gesù Children Hospital (IRCCS), Italy
Reviewed by: Bruno Vincenzi, Campus Bio-Medico University, Italy; Michela Casanova, Fondazione IRCCS Istituto Nazionale dei Tumori, Italy
*Correspondence: Lixia Lu,
This article was submitted to Pediatric Oncology, a section of the journal Frontiers in Oncology
†These authors have contributed equally to this work
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
The present study aimed to explore the optimal chemotherapy strategy for locoregionally advanced children and adolescent nasopharyngeal carcinoma (LcaNPC), based on the level of pretreatment plasma Epstein-Barr virus DNA (pEBV-DNA) in the era of intensity modulated radiation therapy (IMRT).
This real-world, retrospective study consecutively reviewed locoregionally advanced nasopharyngeal carcinoma patients younger than 22 years old from 2006 to 2016 in the Sun Yat-sen University Cancer Center. The Kaplan–Meier method with the log-rank test and the Cox regression model were used to investigate the survival outcomes of different chemotherapy intensities and pEBV-DNA. Treatment-related toxicity was also evaluated using the chi-squared test or Fisher’s exact test.
A total of 179 patients were enrolled, including 86 patients in the high-risk group (pEBV-DNA ≥7,500 copies/ml) and 93 patients in the low-risk group (pEBV-DNA <7,500 copies/ml). Among all patients, those receiving low intensity induction chemotherapy (IC courses = 2) had a better 5-year overall survival (OS) than those receiving no IC (P = 0.025) and high intensity IC (IC courses >2) (P = 0.044). In the high-risk group, receipt of low intensity IC showed significant 5-year OS (P = 0.032), progression-free survival (PFS) (P = 0.027), and 5-year distant metastasis-free survival (DMFS) (P = 0.008) benefits compared with not receiving IC. Multivariate analyses identified that not receiving IC was a risk factor compared with low intensity IC for OS (hazard ratio (HR) = 10.933, P = 0.038) among all patients. Moreover, in the high-risk group, not receiving IC was a risk factor for 5-year OS (HR = 10.878, P = 0.038), 5-year PFS (HR = 5.705, P = 0.041), and 5-year DMFS (HR = 10.290, P = 0.040) compared to low intensity IC. There were no differences in survival for patients treated with or without concurrent chemotherapy.
Two courses of platinum-based IC might be the optimal induction chemotherapy intensity to reduce risk of death, progression, and distant metastasis in patients with high pEBV-DNA levels.
Children and adolescent nasopharyngeal carcinoma (CaNPC) is a rare malignant tumor that accounts for 1–2% of all nasopharyngeal carcinoma (NPC) in endemic areas (
Induction chemotherapy (IC) combined with concurrent chemoradiotherapy (CCRT) has been the standard treatment for locoregionally advanced NPC in adults based on two large-scale prospective studies (
Epstein-Barr virus (EBV) infection, which is known to be related to adult NPC, also plays an important role in prognosis of CaNPC (
Consecutive records of patients with non-distant metastatic nasopharyngeal carcinoma (age ≤21 years old) were reviewed from January 2006 to December 2016 in the Sun Yat-sen Cancer Center. The records were collected independently from the case management system in our institution by two oncologists. Patients were pooled according to the following inclusion criteria: (1) Newly histologically diagnosed nasopharyngeal carcinoma; (2) locoregional advanced stage (III and IVa, according to the AJCC 8th edition stage system); (3) who received radical IMRT; and (4) with known pretreatment pEBV-DNA concentrations. Non-platinum based concurrent chemotherapy were excluded, which is considered a nonstandard therapy regime in our institution. This study was approved by the Institutional Review Board and the Research Ethics Committee of Sun Yat-sen University Cancer Center. Written informed consent to participate in this study was provided by the participants’ legal guardians or next of kin.
All patients received radical IMRT at our institution, the details of which were described previously (
All patients were restaged independently according to the 8th edition of the International Union Against Cancer/AJCC tumor-node-metastasis (TNM) staging system by two oncologists. Treatment-related toxicities were assessed according to the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE 4.0). After treatment, all patients were followed up every 3 months during the first 2 years, every 6 months during the next 3 years, and then annually.
The patients’ pEBV-DNA concentrations were measured using quantitative real-time PCR (qPCR) before therapy (
According to IC courses, patients were divided into three groups: The no IC group, the low intensity IC group (IC courses = 2), and the high intensity IC group (IC courses = 3 or 4).
Overall survival (OS) was calculated from the beginning of therapy to death from any cause. Progression-free survival (PFS) was calculated from the beginning of therapy to recurrence or distant metastasis or death from any cause, whichever came first, and distant metastasis-free survival (DMFS), which was calculated from the beginning of therapy to first distant metastasis.
Survival analyses were conducted using the Kaplan–Meier method with the log-rank test. A Cox proportional hazards model was used for multivariate analysis with calculation of the hazard ratio (HR) and 95% confidence intervals (CIs). A chi-squared test (or Fisher’s exact test) was used to compare acute adverse events and late toxicities during treatment between the different treatment groups. A two-side
A total of 335 patients were screened, and 179 patients were finally included in this study. The baseline characteristics of the patients are listed in
Baseline characteristics of the patients.
All patients(n, %) | Low risk group(pEBV-DNA < 7,500 copies/ml) (n, %) | High risk group(pEBV-DNA ≥ 7,500 copies/ml) (n, %) |
|
|
---|---|---|---|---|
Age | 0.590 | |||
≤17 years | 87 (48.6) | 47 (50.5) | 40 (46.5) | |
>17 years | 92 (51.4) | 46 (49.5) | 46 (53.5) | |
Sex | 0.103 | |||
Male | 136 (76.0) | 66 (71.0) | 70 (81.4) | |
Female | 43 (24.0) | 27 (29.0) | 16 (18.6) | |
Histopathology | 1.000 | |||
WHO II | 3 (1.8) | 2 (2.2) | 1 (1.2) | |
WHO III | 176 (98.3) | 91 (97.8) | 85 (98.8) | |
T stage | 0.135 | |||
T1–3 | 130 (72.6) | 72 (77.4) | 58 (67.4) | |
T4 | 49 (27.4) | 21 (22.6) | 28 (32.6) | |
N stage | 0.041 | |||
N0–1 | 49 (27.4) | 31 (33.3) | 17 (19.8) | |
N2–3 | 130 (72.6) | 62 (66.7) | 69 (80.2) | |
Overall stage | 0.010 | |||
III | 109 (60.3) | 65 (69.9) | 44 (51.2) | |
IVa | 70 (61.5) | 28 (30.1) | 42 (48.8) | |
RT combined chemotherapy | 0.160 | |||
IC | 23 (12.8) | 16 (17.2) | 7 (8.1) | |
IC+C C | 119 (66.5) | 56 (60.2) | 63 (73.3) | |
CC | 34 (19.0) | 20 (21.5) | 14 (16.3) | |
RT alone | 3 (1.7) | 1 (1.1) | 2 (2.3) | |
IC regimes | 0.680 | |||
PF | 37 (25.8) | 17 (23.3) | 20 (28.6) | |
TP | 28 (19.6) | 16 (21.9) | 12 (17.1) | |
TPF | 70 (49.0) | 37 (50.7) | 33 (47.1) | |
GP | 8 (5.6) | 3 (4.1) | 5 (7.2) | |
CC | 0.138 | |||
Yes | 153 (85.5) | 76 (81.7) | 77 (89.5) | |
No | 26 (14.5) | 17 (18.3) | 9 (10.5) | |
I.C intensity | 0.247 | |||
No IC | 36 (20.1) | 20 (21.5) | 16 (18.6) | |
Low intensity IC | 69 (38.5) | 40 (43.0) | 29 (33.7) | |
High intensity IC | 74 (41.3) | 33 (35.5) | 41 (47.7) | |
Dose | 0.886 | |||
≤68Gy | 78 (43.6) | 41 (44.1) | 37 (43.0) | |
>68Gy | 101 (56.4) | 52 (55.9) | 49 (57.0) |
pEBV-DNA, pretreatment plasma EBV DNA; IC, induction chemotherapy; CC, concurrent chemotherapy; RT, radiotherapy.
The cut-off date of follow-up was July 1, 2019. The median follow-up time was 56.1 months (range, 3.3–141.1 months). Among all 179 patients, 11 patients died, and 18 patients suffered from distant metastasis. Only three patients experienced locoregional recurrence. Among the patients with distant metastasis, six patients had bone metastasis, two patients had lung metastasis, one patient had liver metastasis, and nine patients had multiple site metastasis. Among patients with recurrent disease, one patient had nasopharyngeal recurrence, one patient experienced regional lymph node relapse, and one patient experienced both. The 1-year, 3-year, and 5-year OS rates were 98.9, 94.7, and 92.6%, respectively. The 1-year, 3-year, 5-year PFS rates and DMFS rates were 93.3 and 93.9%, 89.8 and 90.9%, and 88.4 and 90.2%, respectively.
Patients with a low pEBV-DNA level had a significantly better 5-year OS than those with a high pEBV-DNA level (98.9
Kaplan–Meier survival curves of CaNPC in different risk groups based on pEBV-DNA
Among the three IC intensity groups, patients in the low IC intensity group had a better 5-year OS than those in the no IC group (98.0
Kaplan–Meier survival curves for 179 patients with NPC stratified by intensity of induction chemotherapy
Univariate and multivariate analyses of 5-year OS, PFS, and DMFS among all patients are listed in
Univariate and multivariate analysis for potential prognostic factors in clinical outcomes among all patients and patients in the high risk group.
Characters | 5-yr OS | 5-yr PFS | 5-yr DMFS | ||||||
---|---|---|---|---|---|---|---|---|---|
|
|
HR (95% CI) |
|
|
HR (95% CI) |
|
|
HR (95% CI) | |
|
|||||||||
Sex | 0.796 | 0.358 | 0.940 | 0.525 | 0.965 | 0.481 | |||
Male | 1 | 1 | 1 | ||||||
Female | 1.910 (0.481–7.585) | 1.405 (0.492–4.012) | 1.525 (0.472–4.930) | ||||||
Age | 0.781 | 0.657 | 0.586 | 0.569 | 0.751 | 0.644 | |||
≤17 yr | 1 | 1 | 1 | ||||||
>17 yr | 0.739 (0.195–2.803) | 0.766 (0.305–1.920) | 0.785 (0.281–2.193) | ||||||
T stage | 0.910 | 0.522 | 0.452 | 0.520 | 0.293 | 0.461 | |||
T1-3 | 1 | 1 | 1 | ||||||
T4 | 0.636 (0.159–2.542) | 1.369 (0.526–3.563) | 1.491 (0.515–4.319) | ||||||
N stage | 0.219 | 0.960 | 0.469 | 0.614 | 0.356 | 0.465 | |||
N0-1 | 1 | 1 | 1 | ||||||
N2-3 | 2.9E5 (0.00–2.33E217) | 1.345 (0.425–4.259) | 1.644 (0.433–6.249) | ||||||
pEBV-DNA | 0.003 | 0.030 | 0.030 | 0.067 | 0.011 | 0.048 | |||
<7500 copies/ml | 1 | 1 | 1 | ||||||
≥7500 copies/ml | 10.103 (1.250–81.680) | 2.558 (0.937–6.985) | 3.325 (1.009–10.470) | ||||||
IC intensity | 0.078 | 0.069 | 0.162 | 0.162 | 0.153 | 0.153 | |||
Low intensity | 1 | 1 | 1 | ||||||
No IC | 0.025a | 0.024a | 13.722 (1.422–132.426) | 0.143a | 0.143a | 3.203 (0.819–12.523) | 0.072a | 0.072a | 3.887 (0.861–17.547) |
High intensity | 0.044b | 0.130b | 5.204 (0.613–44.149) | 0.057b | 0.057b | 2.509 (0.814–8.306) | 0.076b | 0.076b | 2.772 (0.731–10.508) |
CC | 0.574 | 0.747 | 0.921 | 0.480 | 0.600 | 0.989 | |||
Yes | 0.697(0.078–6.238) | 0.628 (0.172–2.287) | 0.989 (0.206–4.750) | ||||||
No | 1 | 1 | 1 | ||||||
|
|||||||||
Sex | 0.234 | 0.339 | 0.733 | 0.507 | 0.630 | 0.340 | |||
Male | 1 | 1 | 1 | ||||||
Female | 1.975 (0.489–7.994) | 1.578 (0.411–6.058) | 1.1.952 (0.494–7.706) | ||||||
Age | 0.961 | 0.679 | 0.899 | 0.836 | 0.884 | 0.994 | |||
≤17 yr | 1 | 1 | 1 | ||||||
>17 yr | 0.748 (0.189–2.963) | 0.888 (0.290–2.721) | 0.995 (0.290–3.417) | ||||||
T stage | 0.136 | 0.491 | 0.534 | 0.821 | 0.150 | 0.901 | |||
T1–3 | 1 | 1 | 1 | ||||||
T4 | 0.611 (0.150–2.482) | 1.250 (0.384–4.073) | 0.968 (0.271–3.454) | ||||||
N stage | 0.279 | 0.969 | 0.368 | 0.830 | 0.670 | 0.739 | |||
N0–1 | 1 | 1 | 1 | ||||||
N2–3 | 3.02E5 (0.0–1.40E281) | 1.055 (0.262–4.257) | 2.335 (0.0.432–12.612) | ||||||
IC intensity | 0.118 | 0.118 | 0.095 | 0.095 | 0.039 | 0.039 | |||
Low intensity | 1 | 1 | 1 | ||||||
No IC | 0.037a | 0.037a | 10.878 (1.135–104.273) | 0.027a | 0.027a | 5.705 (1.073–30.340) | 0.028a | 0.028a | 10.290 (1.115–94.968) |
High intensity | 0.137b | 0.137b | 3.758 (0.430–32.854) | 0.179b | 0.179b | 2.821 (0.569–13.985) | 0.072b | 0.072b | 5.584 (0.676–46.151) |
CC | 0.279 | 0.979 | 0.582 | 0.449 | 0.268 | 0.645 | |||
Yes | 1.32E5 (0.00–NA) | 0.526 (0.100–2.771) | 0.541 (0.095–3.071) | ||||||
No | 1 | 1 | 1 |
P1 is the p value for univariate analysis, P2 is the p value for multivariate analysis, HR, hazard ratio; CI, confidence interval; IC, induction chemotherapy; CC, concurrent chemotherapy; RT, radiotherapy; pEBV-DNA, plasma Epstein-Barr virus DNA; OS, overall survival; PFS, progression-free survival; DMFS, distant metastasis-free survival.
a is the comparison between the low IC intensity group and the no IC group, b is the comparison between the low IC intensity group and the high IC intensity group.,
The characteristics of the patients in two risk groups are listed in
Kaplan–Meier survival curves for the subgroup of 86 patients with NPC in the high-risk group stratified by intensity of induction chemotherapy
In the low risk group, there were no significant differences for 5-year OS, 5-year PFS, and 5-year DMFS in the comparison of the IC intensity groups or with/without CC groups (
Kaplan–Meier’s survival curves for the subgroup of 93 patients with NPC in the low risk group stratified by intensity of induction chemotherapy
Univariate and multivariate analysis for potential prognostic factors in clinical outcomes for patients in the low risk group.
Characters | 5-yr OS | 5-yr PFS | 5-yr DMFS | ||||||
---|---|---|---|---|---|---|---|---|---|
|
|
HR (95% CI) |
|
|
HR (95% CI) |
|
|
HR (95% CI) | |
Sex | 0.514 | 0.581 | 0.899 | 0.889 | 0.824 | 0.652 | |||
Male | 1 | 1 | 1 | ||||||
Female | 0.023 (0.000–1.54E4) | 0.884 (0.155–5.035) | 0.574 (0.051–6.423) | ||||||
Age | 0.312 | 0.642 | 0.412 | 0.679 | 0.321 | 0.657 | |||
≤17 yr | 1 | 1 | 1 | ||||||
>17 yr | 0.011 (0.000–1.93E6) | 0.692 (0.121–3.946) | 0.588 (0.056–6.145) | ||||||
T stage | 0.573 | 0.967 | 0.319 | 0.392 | 0.029 | 0.299 | |||
T1–3 |
1 |
1 |
1 |
||||||
N stage | 0.468 | 0.653 | 0.296 | 0.340 | 0.618 | 0.509 | |||
N0–1 | 1 | 1 | 1 | ||||||
N2–3 | 106.04 (0.000–7.29E10) | 3.038 (0.309–29.823) | 2.331 (0.189–28.681) | ||||||
IC intensity | 0.387 | 0.891 | 0.182 | 0.435 | 0.554 | 0.736 | |||
Low intensity | 1 | 1 | 1 | ||||||
No IC | NAa | 0.882a | 47.686 (0.000–7.84E23) | 0.332a | 0.978a | 0.000 (0.000–NA) | 0.332a | 0.985a | 0.000 (0.000–NA) |
High intensity | 0.254b | 0.634b | 261.50 (0.000–2.41E14) | 0.238b | 0.154b | 3.739 (0.611–22.8) | 0.804b | 0.433b | 2.483 (0.255–24.179) |
P1 is the p value for univariate analysis, P2 is the p value for multivariate analysis, HR, hazard ratio; CI, confidence interval; IC, induction chemotherapy; CC, concurrent chemotherapy; RT, radiotherapy; pEBV-DNA, plasma Epstein-Barr virus DNA; OS, overall survival; PFS, progression-free survival; DMFS, distant metastasis-free survival.
a is the comparison between low IC intensity group and no IC group. b is the comparison between low IC intensity group and high IC intensity group.
Acute adverse events were assessed in all 179 patients (
Cumulative acute adverse events during therapy by maximum grade per patient during therapy.
Adverse event | No IC (n=36) | Low intensity IC (n=69) | High intensity IC (n=74) |
|
|
||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
(toxicity grade) | 1 | 2 | 3 | 4 | 1–4 | 3–4 | 1 | 2 | 3 | 4 | 1–4 | 3–4 | 1 | 2 | 3 | 4 | 1–4 | 3–4 | |||
(%) | (%) | (%) | (%) | (%) | (%) | (%) | (%) | (%) | (%) | (%) | (%) | (%) | (%) | (%) | (%) | (%) | (%) | ||||
Leucocytope- nia | 12 | 11 | 8 | 0 | 31 | 8 | 11 | 28 | 20 | 2 | 61 | 22 | 13 | 41 | 18 | 0 | 72 | 18 | 0.046 | 0.467 | |
(33.3) | (30.6) | (22.2) | (0.0) | (86.1) | (22.2) | (15.9) | (40.6) | (28.2) | (2.8) | (88.4) | (31.9) | (17.6) | (55.4) | (24.3) | (0.0) | (97.3) | (24.3) | ||||
Neutropenia | 4 | 6 | 4 | 0 | 14 | 4 | 14 | 21 | 12 | 5 | 52 | 17 | 12 | 20 | 22 | 10 | 69 | 32 | 0.000 | 0.001 | |
(11.1) | (16.7) | (11.1) | (0.0) | (38.9) | (11.1) | (20.3) | (30.4) | (17.4) | (7.2) | (75.3) | (24.6) | (16.2) | (27.0) | (29.7) | (13.5) | (93.2) | (43.2) | ||||
Anemia | 21 | 4 | 1 | 0 | 26 | 1 | 36 | 15 | 4 | 0 | 55 | 4 | 49 | 17 | 2 | 0 | 68 | 2 | 0.021 | 0.610 | |
(58.3) | (11.1) | (2.8) | (0.0) | (72.2) | (2.8) | (52.2) | (21.7) | (5.8) | (0.0) | (79.7) | (5.8) | (66.2) | (23.0) | (2.7) | (0.0) | (91.9) | (2.7) | ||||
Thrombocyto- penia | 5 | 3 | 0 | 0 | 8 | 0 | 7 | 10 | 0 | 0 | 17 | 0 | 5 | 9 | 2 | 0 | 16 | 2 | 0.907 | 0.356 | |
(13.9) | (8.3) | (0.0) | (0.0) | (22.2) | (0) | (10.1) | (14.5) | (0.0) | (0.0) | (24.6) | (0) | (6.8) | (12.2) | (2.7) | (0.0) | (21.6) | (2.7) | ||||
AST increase | 1 | 0 | 0 | 0 | 1 | 0 | 18 | 0 | 0 | 0 | 18 | 0 | 18 | 0 | 1 | 0 | 19 | 1 | 0.010 | 1.000 | |
(2.8) | (0.0) | (0.0) | (0.0) | (2.8) | (0) | (26.1) | (0.0) | (0.0) | (0.0) | (26.1) | (0) | (24.3) | (0.0) | (1.4) | (0.0) | (25.7) | (1.4) | ||||
ALT increase | 10 | 1 | 0 | 0 | 11 | 0 | 26 | 7 | 1 | 0 | 34 | 1 | 35 | 9 | 1 | 0 | 45 | 1 | 0.012 | 1.000 | |
(27.8) | (2.8) | (0.0) | (0.0) | (30.6) | (0) | (37.7) | (10.1) | (1.4) | (0.0) | (49.3) | (1.4) | (47.3) | (12.2) | (1.4) | (0.0) | (60.8) | (1.4) | ||||
BUN increase | 5 | 1 | 0 | 0 | 6 | 0 | 10 | 0 | 0 | 0 | 10 | 0 | 16 | 0 | 1 | 0 | 17 | 1 | 0.228 | 1.000 | |
(13.9) | (2.8) | (0.0) | (0.0) | (16.7) | (0) | (14.5) | (0.0) | (0.0) | (0.0) | (14.5) | (0) | (21.6) | (0.0) | (1.4) | (0.0) | (23.0) | (1.4) | ||||
Mucositis | 10 | 9 | 4 | 0 | 23 | 4 | 13 | 17 | 7 | 0 | 37 | 7 | 12 | 16 | 6 | 0 | 34 | 6 | 0.204 | 0.856 | |
(27.8) | (25.0) | (11.1) | (0) | (63.9) | (25.0) | (18.8) | (24.6) | (10.1) | (0) | (53.6) | (10.1) | (16.2) | (21.6) | (8.1) | (0) | (45.9) | (8.1) | ||||
Dermatitis | 6 | 1 | 0 | 0 | 7 | 1 | 20 | 3 | 1 | 0 | 24 | 1 | 10 | 3 | 1 | 0 | 14 | 1 | 0.062 | 0.636 | |
(16.7) | (2.8) | (0) | (0) | (19.4) | (2.8) | (29.0) | (4.3) | (1.4) | (0) | (34.8) | (1.4) | (13.5) | (4.1) | (1.4) | (0) | (18.9) | (1.4) | ||||
Vomiting | 13 | 5 | 0 | 0 | 18 | 0 | 34 | 6 | 1 | 0 | 41 | 1 | 47 | 6 | 1 | 0 | 54 | 1 | 0.046 | 0.636 | |
(36.1) | (13.9) | (0) | (0) | (50.0) | (0) | (49.3) | (8.7) | (1.4) | (0) | (59.4) | (1.4) | (64.5) | (8.1) | (1.4) | (0) | (73.0) | (1.4) |
Late toxicities were assessed in 168 patients (late toxicities could not be assessed in the 11 patients who died) (
Radiotherapy-related grade 2–4 late toxicities.
Late toxicities | No IC (n = 32,%) | Low intensity IC (n = 68,%) | High intensity IC (n = 68,%) |
|
|
---|---|---|---|---|---|
(grade 2–4) | |||||
Xerostomia | 12 (37.5) | 23 (33.8) | 23 (33.8) | 0.925 | |
Hearing impairment | 8 (25.0) | 16 (23.5) | 14 (20.6) | 0.884 | |
Neck fibrosis | 7 (21.9) | 14 (20.6) | 15 (22.1) | 0.976 | |
Chronic otitis | 4 (12.5) | 9 (13.2) | 10 (14.7) | 0.947 | |
Trismus | 3 (9.3) | 7 (10.2) | 5 (7.4) | 0.828 | |
Eye damage | 3 (9.3) | 3 (4.4) | 7 (10.3) | 0.384 | |
Endocrine dysfunction | 3 (9.3) | 4 (5.9) | 3 (4.4) | 0.640 | |
Temporal lobe injury | 3 (9.3) | 5 (7.4) | 1 (1.5) | 0.127 |
As far as we know, the efficacy of IC has not been evaluated well in locoregionally advanced CaNPC in the IMRT era and a standard combined chemotherapy strategy has also not been established. In the present real-world study with a large number of consecutive patients, we found that low intensity IC (two courses of platinum-based IC) was the optimal intensity of IC to reduce the risk of death, progression, and distant metastasis in patients with high pretreatment pEBV-DNA levels; however, there was no optimal IC intensity for patients with low pEBV-DNA.
The patients in our study achieved a satisfactory 5-year OS rate (92.6%), which was higher compared with that reported in a previous study from the same institution (86.6% in the IC +CCRT group and 80.2% in the CCRT group) (
IC followed by CCRT had been widely accepted as the standard treatment strategy for locoregionally advanced NPC in adults, based on two large-scale prospective, multicenter, randomized phase III clinical trials (
Pretreatment pEBV-DNA is an important biomarker to predict survival and guide treatment for adults with NPC (
Concurrent cisplatin chemotherapy during radiotherapy has been the standard treatment for locoregional advanced NPC for twenty years, following the publication of the phase 3 randomized intergroup study 0099 (
The limitations of this study were mainly related to its retrospective nature. First, this was a single-center retrospectively non-randomized study and potential confounding factors might bias the results. Consequently, we conducted multivariate analyses to weaken these confounding effects. Second, the IC regimens varied because they were extracted directly from electronic records rather than decided upon by the authors. Based on this consideration, the aim of this study did not include determining the best IC regimen. Moreover, an international randomized, phase II study showed that patients with CaNPC treated with the IC regimes TPF or PF had no difference in survival (
The two courses of platinum-based IC might be the optimal chemotherapy intensity to reduce risk of death, progression, and distant metastasis in patients with high pEBV-DNA levels. Higher intensity IC increased toxicity without any survival benefit.
The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.
The studies involving human participants were reviewed and approved by Institutional Review Board and the Research Ethics Committee of Sun Yat-sen University Cancer Center. Written informed consent to participate in this study was provided by the participants
LL, ZZ, and CC designed the study. ZZ, GL, ZC, and YH collected the data. All authors discussed the data. ZZ and CC drafted the manuscript. All authors contributed to the article and approved the submitted version.
This study was funded by the Planned Science and Technology Project of Guangdong Province (grant no. 2016A020215085) and the 308 Clinical Research Funding of Sun Yat-sen University Cancer Center (grant no. 308-2015-011).
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
LcaNPC, locoregionally advanced children and adolescent nasopharyngeal carcinoma; CaNPC, children and adolescent nasopharyngeal carcinoma; NPC, nasopharyngeal carcinoma; pEBV-DNA, plasma Epstein-Barr virus DNA; IMRT, intensity modulated radiation therapy; 2D-CRT, two-dimensional conventional radiotherapy; IC, induction chemotherapy; CC, concurrent chemotherapy; CCRT, concurrent chemoradiotherapy.