Abstract
Background
To compare the differences in long-term quality of life (QoL) between survivors of paediatric and adult patients with nasopharyngeal carcinoma (NPC) and assess the clinical factors that predict long-term QoL.
Methods
We enrolled 420 long-term NPC survivors who were alive for at least 8 years after treatment, including 195 paediatric and 225 adult patients diagnosed and treated with intensity-modulated radiotherapy (IMRT) at Sun Yat-sen University Cancer Centre (SYSUCC) between 2011 and 2015. Data on clinical factors and EORTC QLQ-C30 were collected from all participants. The QoL of paediatric and adult NPC survivors was compared.
Results
The paediatric group had significantly better outcomes in global health status (paediatric: 80.2 ± 12.7; adult: 77.2 ± 11.5; P = 0.027), physical function (paediatric: 98.5 ± 4.6; adult: 95.1 ± 7.0; P < 0.001), role function (paediatric: 97.0 ± 9.2; adult: 90.5 ± 15.2; P < 0.001), social function (paediatric: 96.0 ± 8.9; adult: 93.5 ± 11.8; P = 0.038), insomnia (paediatric: 1.9 ± 7.8; adult: 13.1 ± 22.3; P < 0.001), constipation (paediatric: 1.3 ± 7.5; adult: 8.0 ± 17.4; P < 0.001), diarrhea (paediatric: 0.7 ± 4.6; adult: 2.8 ± 9.3; P = 0.010), and financial difficulties (paediatric: 1.9 ± 7.8; adult: 11.0 ± 19.8; P < 0.001), but poorer cognitive function (paediatric: 88.3 ± 9.9; adult: 93.8 ± 12.6; P < 0.001) than the adult group. Pretreatment clinical factors, including T stage, N stage, and pre-treatment EBV (Epstein-Barr Virus) DNA, showed a strong association with QoL. However, the factors that affected the QoL outcomes differed between the two groups. In survivors of paediatric cancer, global health status/QoL was strongly correlated with T stage (P < 0.001) and clinical stage (P = 0.018), whereas it was strongly correlated with pre-treatment EBV DNA (P = 0.008) in adults.
Conclusion
Paediatric survivors of NPC have a significantly better QoL than adult NPC survivors. Moreover, pre-treatment T stage, N stage, and EBV DNA significantly influenced the overall health status of the survivors. These results highlight the need to tailor care to both age groups to promote better long-term health outcomes.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12885-024-12966-4.
Keywords: Nasopharyngeal carcinoma (NPC), Long-term quality of life, Paediatric NPC, Adult NPC, Cancer survivors
Background
Nasopharyngeal carcinoma (NPC) has become an epidemic in Southern China and Southeast Asia. Since NPC occurs in an obscured location and the clinical symptoms of patients are nonspecific, most individuals are diagnosed at locally advanced stages [1]. Radiotherapy (RT) combined with chemotherapy is recommended for patients with locally advanced NPC, significantly improving the outcome of long-term survival for patients with NPC [2, 3]. The incidence of NPC tends to peak between the ages of 40 and 60 years, with sub-peak between the ages of 10 and 20 [4]. Notably, NPC is not commonly observed in paediatric patients, accounting for only 2% of cases [5]. The clinicopathological and prognostic features of paediatric NPC differ from those of adult NPC [6–8]. Additionally, late sequelae and long-term survival outcomes diverge between paediatric and adult NPC patients [9–13].
As the high overall survival rate of patients with NPC continues to rise, the long-term QoL of survivors is becoming an important indicator that cannot be ignored [14]. Most studies have reported on the QoL of cancer survivors from three months to five years after treatment for many cancers, such as oral and ovarian cancers, and the impact of cancer on a patient’s QoL has been reported to last up to eight years [15–18]. Several previous studies have investigated the QoL and associated factors in patients with NPC and head and neck cancer after treatment, with an increasing focus on the assessment of QoL in NPC survivors [19]. However, these studies have only examined the QoL of adult survivors individually over five years after treatment and did not focus on long-term QoL. Furthermore, no studies have reported on the long-term QoL of paediatric NPC survivors and compared the QoL for survivors of paediatric and adult NPC patients.
Therefore, our study is the first to investigate the long-term QoL in survivors of paediatric and adult NPC patients. The main purpose of this study was to compare the differences between these two survivor groups and evaluate the clinical factors that significantly affect various aspects of their QoL.
Methods
Patients
We recruited 458 long-term survivors of nasopharyngeal cancer who survived at least 8 years after treatment at the Sun Yat-sen University Cancer Control Centre (SYSUCC), including 209 paediatric patients and 249 adult patients diagnosed with nasopharyngeal cancer between 2011 and 2015 [16]. Based on previous studies, paediatric patients were defined as those who were under 21 years of age at diagnosis [7, 20]. The inclusion criteria were as follows: (1) pathologically confirmed diagnosis of NPC, (2) primarily untreated and non-metastatic cases, (3) treatment with intensity-modulated radiotherapy (IMRT), and (4) cooperation with the follow-up via telephone. The exclusion criteria were as follows: (1) death, tumour recurrence, or metastasis after treatment; (2) unable to collect current quality of life questionnaires; and (3) serious discrepancies in the results of the questionnaire. All of the patient quality of life assessments in our study were completed in 2023. Finally, the study included 420 individuals (195 paediatric and 225 adult) who had no disease progression and were able to complete the questionnaire at least 8 years after treatment. Disease progression was defined as recurrence at the primary site, cervical lymph nodes, or metastases elsewhere [21]. To balance the influence of covariates and decrease potential bias, we used propensity score matching (PSM) to match paediatric and adult patients with NPC at a ratio of 1:1 [22]. Ultimately, 155 survivors of paediatric and adult NPC patients were included in the subsequent analyses. Eligible patients underwent systematic examination before treatment, and all patients were reclassified for TNM staging based on clinical and imaging data according to the 8th edition of the American Joint Committee on Cancer staging system (AJCC). The Ethics Committee of the SYSUCC approved the study protocol, and written informed consent was obtained from all participants. The flow diagram is shown in Fig. 1.
Fig. 1.
Flow diagram
Data collection and questionnaires
Pretreatment evaluations were routinely performed on all patients, including clinical history and physical examination; nasoendoscopy and biopsy; liver and renal function tests; whole-body bone scan; abdominal ultrasonography; and computed tomography (CT), magnetic resonance imaging (MRI) of the head and neck, or positron emission tomography/computed tomography (PET-CT). We retrospectively collected data on patients clinical characteristics including age, gender, TNM stage, treatment, pathological type, family history of NPC, RT techniques, and pre-treatment EBV DNA levels. A real-time polymerase chain reaction assay was used to analyse EBV DNA levels in the plasma [23, 24]. The patients completed the questionnaire with the help of a trained interviewer over the phone and at regular follow-up appointments. A total of 420 questionnaires (195 from paediatric patients and 225 from adult patients) were collected after at least three attempts to contact the patient.
QoL assessments
The Chinese version of the standardised 30-item EORTC QLQ-C30 (version 3.0) is a valid tool for assessing the QoL in Chinese patients with cancer, including adult and paediatric patients with cancer [25–27]. This questionnaire contains 15 dimensions, including functional dimensions: physical functioning (PF), role functioning (RF), emotional functioning (EF), cognitive functioning (CF), and social functioning (SF); 1 dimension of global health status/QoL; symptom dimensions: fatigue, nausea and vomiting, pain, dyspepsia, insomnia, appetite loss, constipation, diarrhoea, and financial difficulties [28]. The score of the items included in each dimension was added and divided by the number of items to obtain an approximate score of the dimension, and then the approximate score was converted into a standardised score of 0 to 100. For the functioning and global health status/QoL scales, a higher score indicated better health, whereas on the symptom scales, a higher score indicated a higher level of symptom burden.
Radiotherapy
All patients received IMRT at our centre once daily, five times per week. Patients with NPC received a high dose of radiation to the nasopharynx and affected neck lymph nodes, and a moderate dose of radiation to the unaffected nodes and surrounding tissues. Adult patients with NPC received a total dose of 68–75 Gy at 2.0–2.5 Gy/fraction to the primary tumour within the planned target volume (PTV) during RT. Paediatric patients with NPC received a total dose of 57–74 Gy at 1.8–2.4 Gy/fraction to the primary tumour within the PTV during RT. The details of RT in both adult and paediatric patients are presented in an article published by our centre [9].
Chemotherapy
Patients diagnosed with clinical stage I cancer received RT alone, whereas those diagnosed with stages II–IVA cancer were treated with either concurrent chemoradiotherapy (CCRT) or induction chemotherapy (IC) + CCRT. Overall, 223 (53.1%) patients received IC followed by CCRT, and 162 (38.6%) received only CCRT. IC was administered for 21 days per cycle for 2–3 cycles. Platinum-based regimens included paclitaxel/docetaxel with cisplatin (TP), paclitaxel/docetaxel plus cisplatin with 5-fluorouracil (TPF), fluorouracil with cisplatin (PF), and gemcitabine with cisplatin (GP). Concurrent cisplatin chemotherapy was administered at a dose of 80–100 mg/m2 each cycle for a total–2–3 cycles.
Follow-up
For the first three years, the patients were examined every three months, then every six months for the following two years, and annually thereafter. Physical examination, nasopharyngoscopic examination, MRI of the nasopharynx and neck, chest radiography, abdominal ultrasonography, and EBV DNA tests were performed at each follow-up visit. Disease progression was defined as recurrence at the primary site, in the cervical lymph nodes, or metastases to other body sites. In this study, the follow-up period was calculated from the first day of treatment to the collection of telephonic questionnaires. The final follow-up date was 29 April 2023.
Statistical methods
All analyses were performed using the R software (version 4.2.1) and SPSS software (version 27.0; SPSS Inc., Chicago, III, USA). Descriptive statistics are presented as mean ± standard deviation (SD), median (interquartile range), or frequency (percentage). PSM was computed for each patient at a 1:1 ratio to balance the following covariates: T category, N category, and clinical stage, all of which were imbalanced at baseline. Differences between groups were analysed using T-test for normally distributed continuous data and χ2 test or Fisher’s exact test for categorical data. The Mantel–Haenszel chi-square test and linear regression analysis were used to analyse the correlation between clinical factors and the functional scale [29]. A backward stepwise linear regression analysis was conducted to investigate the factors influencing the outcomes [30]. A statistically significant result was set at P-value ≤ 0.05 level (two-tailed).
Results
There were significant differences in the demographic and clinical characteristics of paediatric and adult patients with NPC (Table 1). Of the 195 survivors of paediatric, 165 (84.6%) went on to complete high school and beyond, and 30 (15.4%) dropped out of school after treatment and did not complete a high school diploma. After PSM, 155 eligible paediatric and 155 matched adult patients were included (Table 1). The median age was 18 years (range, 7–21 years) in the paediatric cohort and 44 years (range, 27–69 years) in the adult cohort. In terms of clinical stage distribution, there were 1 (0.7%) patient with stage I, 9 (5.8%) with stage II, 93 (60.0%) with stage III, and 52 (33.5%) with stage IVA among the survivors of paediatric and adult patients. The prescribed radiation dose to the primary tumour site (median: 68 Gy vs. 70 Gy) and dose per fraction (median: 2.2 Gy/f vs. 2.3 Gy/f) were significantly lower in the paediatric group than in the adult group (P < 0.001).
Table 1.
Comparison of clinical characteristics between paediatric and adult patients before and after using propensity score matching
| Before PSM | After PSM | ||||||
|---|---|---|---|---|---|---|---|
| Paediatric (N = 195) |
Adult (N = 225) |
P | Paediatric (N = 155) |
Adult (N = 155) |
P | ||
| Sex | 0.204 | 0.395 | |||||
| Male | 131 (67.2%) | 165 (73.3%) | 101(65.2%) | 109(70.3%) | |||
| Female | 64 (32.8%) | 60 (26.7%) | 54(34.8%) | 46(29.7%) | |||
| Age at NPC diagnosis, median (range, yr) | 18 (7–21) | 44(27–69) | < 0.001 | 18 (7–21) | 44 (27–69) | < 0.001 | |
| Age at QOL assessment, median (range, yr) | 27 (18–32) | 53 (37–78) | < 0.001 | 27 (18–32) | 53 (37–78) | < 0.001 | |
| Family history of NPC | 0.481 | 0.214 | |||||
| No | 190 (97.4%) | 222 (98.7%) | 150 (96.8%) | 154 (99.3%) | |||
| Yes | 5 (2.6%) | 3 (1.3%) | 5 (3.2%) | 1 (0.7%) | |||
| T stage* | < 0.001 | > 0.999 | |||||
| 1 | 3 (1.5%) | 12 (5.3%) | 3 (2.0%) | 3 (2.0%) | |||
| 2 | 21 (10.8%) | 49 (21.8%) | 21 (13.5%) | 21 (13.5%) | |||
| 3 | 105 (53.8%) | 122 (54.2%) | 93 (60.0%) | 93 (60.0%) | |||
| 4 | 66 (33.9%) | 42 (18.7%) | 38 (24.5%) | 38 (24.5%) | |||
| N stage* | < 0.001 | > 0.999 | |||||
| 0 | 8 (4.1%) | 27 (12.0%) | 7 (4.6%) | 7 (4.6%) | |||
| 1 | 58 (29.7%) | 94 (41.8%) | 58 (37.4%) | 58 (37.4%) | |||
| 2 | 94 (48.2%) | 80 (35.5%) | 69 (44.5%) | 69 (44.5%) | |||
| 3 | 35 (18.0%) | 24 (10.7%) | 21 (13.5%) | 21 (13.5%) | |||
| Clinical stage* | < 0.001 | > 0.999 | |||||
| I | 1 (0.5%) | 6 (2.7%) | 1 (0.7%) | 1 (0.7%) | |||
| II | 9 (4.6%) | 30 (13.3%) | 9 (5.8%) | 9 (5.8%) | |||
| III | 93 (47.7%) | 130 (57.8%) | 93 (60.0%) | 93 (60.0%) | |||
| IVA | 92 (47.2%) | 59 (26.2%) | 52 (33.5%) | 52 (33.5%) | |||
| WHO type | 0.501 | 0.498 | |||||
| I | 0 | 2 (0.9%) | 0 (0.00%) | 2 (1.3%) | |||
| II | 195 (100.0%) | 223 (99.1%) | 155 (100.0%) | 153 (98.7%) | |||
| Pre-EBV DNA# | 0.086 | 0.865 | |||||
| < 4000 | 92 (50.8%) | 115 (60.2%) | 77 (54.2%) | 75 (56.0%) | |||
| ≥ 4000 | 89 (49.2%) | 76 (39.8%) | 65 (45.8%) | 59 (44.0%) | |||
| Treatment modality | 0.117 | 0.760 | |||||
| RT | 11 (5.7%) | 24 (10.7%) | 9 (5.8%) | 11 (7.1%) | |||
| IC + CCRT/RT | 111 (56.9%) | 112 (49.8%) | 82 (52.9%) | 76 (49.0%) | |||
| CCRT | 73 (37.4%) | 89 (39.5%) | 64 (41.3%) | 68 (43.9%) | |||
| RT dose for primary site | |||||||
| Total dose, median (range, Gy) | 68(57–74) | 70 (68–75) | < 0.001 | 68(57–74) | 70 (68–73) | < 0.001 | |
| Dose/fraction, median (range, Gy/f) | 2.2 (1.8–2.4) | 2.3 (2.0-2.5) | < 0.001 | 2.2 (1.8–2.4) | 2.3 (2.0-2.5) | < 0.001 | |
Note Values are presented as numbers of patients with percentage in the parentheses unless otherwise indicated. WHO, World Health Organization; IC, Induction chemotherapy; CCRT, Concurrent chemotherapy; RT, Radiotherapy
*According to the 8th edition of American Joint Committee on Cancer staging system of nasopharyngeal carcinoma. # Data with missing values
Health-related QoL (EORTC QLQ-C30) in the paediatric and adult groups
Paediatric patients had higher scores than adult patients (paediatric: 80.2 ± 12.7; adult: 77.2 ± 11.5; P = 0.027) in global health status/QoL. Furthermore, in the Functional Scale/Items, paediatric patients scored higher in PF (paediatric: 98.5 ± 4.6; adult: 95.1 ± 7.0; P < 0.001), RF (paediatric: 97.0 ± 9.2; adult: 90.5 ± 15.2; P < 0.001), EF (paediatric: 97.0 ± 6.1; adult: 96.5 ± 6.8; P = 0.511), and SF (paediatric: 96.0 ± 8.9; adult: 93.5 ± 11.8; P = 0.038) but worse in CF (paediatric: 88.3 ± 9.9; adult: 93.8 ± 12.6; P < 0.001) than adult patients. Additionally, there were differences in the Symptom scale/items, including insomnia (paediatric: 1.9 ± 7.8; adult: 13.1 ± 22.3; P < 0.001), constipation (paediatric: 1.3 ± 7.5; adult: 8.0 ± 17.4; P < 0.001), diarrhoea (paediatric: 0.7 ± 4.6; adult: 2.8 ± 9.3; P = 0.010), and financial difficulties (paediatric: 1.9 ± 7.8; adult: 11.0 ± 19.8; P < 0.001). Table 2; Fig. 2 presents the results.
Table 2.
Mean and SD for health-related quality of life in each group
| Paediatric(N = 155) | Adult(N = 155) | P | |
|---|---|---|---|
| Global health status/QoL | 80.2 (12.7) | 77.2 (11.5) | 0.027* |
| Functional Scale/Items | |||
| Physical functioning (PF) | 98.5 (4.6) | 95.1 (7.0) | <0.001* |
| Role functioning (RF) | 97.0 (9.2) | 90.5 (15.2) | <0.001* |
| Emotional functioning (EF) | 97.0 (6.1) | 96.5 (6.8) | 0.511 |
| Cognitive functioning (CF) | 88.3 (9.9) | 93.8 (12.6) | <0.001* |
| Social functioning (SF) | 96.0 (8.9) | 93.5 (11.8) | 0.038* |
| Symptom Scale/Items | |||
| Fatigue | 4.4(8.7) | 5.4 (8.3) | 0.301 |
| Nausea and vomiting | 1.2 (4.7) | 0.4 (2.7) | 0.083 |
| Pain | 0.9 (4.2) | 1.5 (6.1) | 0.278 |
| Dyspnoea | 0.9 (5.3) | 1.9 (7.8) | 0.158 |
| Insomnia | 1.9 (7.8) | 13.1 (22.3) | <0.001* |
| Appetite loss | 1.9 (8.7) | 2.8 (10.0) | 0.420 |
| Constipation | 1.3 (7.5) | 8.0 (17.4) | <0.001* |
| Diarrhoea | 0.7 (4.6) | 2.8 (9.3) | 0.010* |
| Financial difficulties | 1.9 (7.8) | 11.0 (19.8) | <0.001* |
Note For the QLQ-C30 and Functional Scale/Items, a higher score indicates better health, while in the Symptom Scale/Items, a higher score indicates a higher level of symptom burden
* Statistically significant result
Fig. 2.
Comparison between paediatric and adult patients with nasopharyngeal carcinoma in the result of health-related quality of life. A QoL and functional domains; B symptom domains. QoL, quality of life
Association between clinical characteristics and health-related QoL in all patients
We conducted an analysis to investigate the relationship between questionnaires and clinical characteristics of patients before treatment and found that global health status/QoL was negatively correlated with T stage (regression coefficient estimate (R)= -0.196, P < 0.001), clinical stage (R= -0.139, P = 0.014), and pre-treatment EBV DNA levels (R= -0.172, P = 0.004). Within the CF, PF and RF were related to pre-treatment EBV DNA levels, while SF was significantly correlated with N stage (R = 0.142, P = 0.012). These findings were further confirmed by univariate analysis of QoL. Table S1 and Figure S1A present the results.
Association between clinical characteristics and health-related QoL in the paediatric and adult subgroups
Considering the differences between the two groups, we performed linear regression analyses in the subgroups and investigated the relationship between the questionnaires and clinical factors. In the paediatric group, the study found that the global health status was associated with T stage (R= -0.276, P < 0.001) and clinical stage (R= -0.191, P = 0.018), while CF was related to T stage (R= -0.279, P < 0.001), N stage (R= -0.198, P = 0.014), and clinical stage (R= -0.316, P < 0.001). Table 3 and Figure S1B present the results. In the adult group, global health status/QoL, PF, and RF were solely associated with pre-treatment EBV DNA levels (QoL: R= -0.228, P = 0.008; PF: R= -0.221, P = 0.010; RF: R= -0.269, P = 0.002). SF was related to N stage (R = 0.243, P = 0.002), and CF was related to a family history of NPC (R= -0.174, P = 0.031). Table 3 and Figure S1C present the results.
Table 3.
Correlation between quality of life and clinical factors in paediatric group (N = 155) and adult group (N = 155)
| Predictors | Global health status/QoL | Physical functioning | Role functioning | Cognitive functioning | Social functioning | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| R | P | R | P | R | P | R | P | R | P | |
| Paediatric | ||||||||||
| Sex | 0.108 | 0.179 | 0.148 | 0.066 | 0.068 | 0.402 | 0.045 | 0.577 | 0.149 | 0.064 |
| Family of NPC | -0.051 | 0.529 | 0.062 | 0.447 | -0.073 | 0.366 | -0.153 | 0.057 | 0.013 | 0.870 |
| T stage | -0.276 | < 0.001* | -0.048 | 0.554 | -0.052 | 0.571 | -0.279 | < 0.001* | -0.079 | 0.331 |
| N stage | -0.067 | 0.407 | 0.112 | 0.164 | -0.003 | 0.968 | -0.198 | 0.014* | 0.013 | 0.872 |
| Clinical stage | -0.191 | 0.018* | -0.008 | 0.926 | -0.091 | 0.260 | -0.316 | < 0.001* | -0.045 | 0.576 |
| EBV DNA | -0.135 | 0.109 | -0.017 | 0.841 | 0.034 | 0.690 | -0.098 | 0.245 | -0.051 | 0.548 |
| WHO type | 0.084 | 0.296 | -0.039 | 0.634 | 0.000 | 0.412 | 0.057 | 0.479 | 0.056 | 0.489 |
| Treatment modality | -0.046 | 0.568 | 0.044 | 0.585 | -0.141 | 0.080 | 0.031 | 0.701 | -0.121 | 0.134 |
| Dose per fraction | 0.044 | 0.602 | -0.057 | 0.497 | -0.028 | 0.736 | -0.056 | 0.506 | -0.138 | 0.098 |
| RT dose | 0.027 | 0.745 | -0.051 | 0.543 | -0.030 | 0.718 | 0.119 | 0.155 | -0.032 | 0.702 |
| Adult | ||||||||||
| Sex | 0.063 | 0.435 | -0.025 | 0.755 | -0.029 | 0.718 | -0.015 | 0.856 | -0.064 | 0.428 |
| Family of NPC | -0.015 | 0.851 | 0.057 | 0.480 | 0.050 | 0.534 | -0.174 | 0.031* | 0.044 | 0.584 |
| T stage | -0.111 | 0.170 | -0.108 | 0.179 | -0.071 | 0.378 | 0.065 | 0.422 | 0.031 | 0.704 |
| N stage | 0.087 | 0.280 | -0.071 | 0.377 | 0.112 | 0.165 | 0.033 | 0.687 | 0.243 | 0.002* |
| Clinical stage | -0.084 | 0.298 | -0.110 | 0.172 | -0.045 | 0.581 | 0.077 | 0.339 | 0.107 | 0.187 |
| EBV DNA | -0.228 | 0.008* | -0.221 | 0.010* | -0.269 | 0.002* | -0.158 | 0.069 | -0.141 | 0.105 |
| WHO type | -0.073 | 0.366 | -0.096 | 0.236 | 0.035 | 0.670 | 0.076 | 0.346 | -0.074 | 0.358 |
| Treatment modality | 0.002 | 0.978 | -0.068 | 0.403 | 0.097 | 0.230 | -0.009 | 0.908 | 0.046 | 0.571 |
| Dose per fraction | 0.038 | 0.638 | 0.007 | 0.935 | 0.014 | 0.859 | -0.024 | 0.769 | -0.089 | 0.272 |
| RT dose | -0.024 | 0.769 | -0.033 | 0.682 | -0.068 | 0.404 | -0.023 | 0.775 | -0.026 | 0.751 |
Abbreviations EORTC European Organization for Research and Treatment of Cancer, QoL Quality of life
* Statistically significant result
Furthermore, to identify the most important predictors of global health status/QoL and CF in the paediatric group, T and N stages, which were meaningful in the single linear regression, were included in the multivariate analysis. The result showed that T stage was significantly related to QoL (T1 vs. T3: P = 0.016; T1 vs. T4: P = 0.013) and CF (T1 vs. T4: P = 0.042). Table 4 presents the results.
Table 4.
Multivariate analysis of the quality of life in paediatric survivors (stepwise backward multivariate linear regression analysis)
| EORTC QLQ-C30 scale/predictor | Unstandardized B | Std.Error | P value | 95% CI | |
|---|---|---|---|---|---|
| Paediatric: global health status/QoL | |||||
| T1 | Reference | ||||
| T2 | -12.179 | 9.267 | 0.191 | -30.343 | 5.984 |
| T3 | -21.296 | 8.733 | 0.016* | -38.413 | -4.180 |
| T4 | -22.500 | 8.910 | 0.013* | -39.964 | -5.036 |
| Paediatric: Cognitive functioning | |||||
| T1 | Reference | ||||
| T2 | -5.018 | 6.918 | 0.470 | -18.577 | 8.540 |
| T3 | -10.993 | 6.506 | 0.094 | -23.745 | 1.759 |
| T4 | -13.690 | 6.647 | 0.042* | -26.717 | -0.663 |
| N0 | Reference | ||||
| N1 | 2.549 | 4.743 | 0.592 | -6.748 | 11.845 |
| N2 | 2.105 | 4.719 | 0.656 | -7.144 | 11.354 |
| N3 | -5.335 | 5.086 | 0.296 | -15.303 | 4.634 |
Abbreviations EORTC European Organization for Research and Treatment of Cancer, QoL Quality of life
The factors included in the stepwise regression were as follows: T stage and N stage
* Statistically significant result
Discussion
Our study is the first to conduct a comparative analysis of the long-term QoL of paediatric and adult patients with NPC, and we found that differences in clinical factors have a significant impact on the QoL of survivors of paediatric and adult patients with NPC. Previous studies have suggested that paediatric patients with NPC have a higher tumour burden at the time of diagnosis but achieve superior survival outcomes and experience less long-term treatment-related toxicity related [6, 9, 12, 13, 31–33]. Our findings indicate that the survivors of paediatric cancer had a significantly higher QoL than adults in most functional and symptomatic domains of the QLQ-C30. Therefore, we can consider paediatric patients with NPC as a unique group compared with adult patients.
Given the high overall survival rate of NPC, it is particularly important to assess the QoL after treatment, especially among long-term survivors, which refers to overall patient satisfaction. First, with continuous improvements in treatments and the therapeutic effects of NPC, the number of people surviving NPC has increased [34]. Second, NPC occurs in an obscure location, and RT, the dominant treatment targeting the adjacent head and neck, usually results in injury after irradiation [9, 19, 31]. Third, recognising differences in the QoL of survivors helps clinicians to target potential late effects for early detection and intervention in routine clinical practice and subsequent follow-ups. For this study, we used only the EORTC QLQ-C30 to assess patients’ quality of life. The QLQ-H&N35, which is commonly used to assess quality of life in head and neck cancer, was not included due to insufficient evidence supporting its suitability for use in paediatric patients. Several previous studies have shown that the QoL of patients with NPC has improved significantly after treatment owing to changes in RT techniques and the promotion of IC [19, 34, 35]. Additionally, there is a significant relationship between QoL and prognosis [36]. Lastrucci et al. found that post-treatment xerostomia and hearing loss have a negative impact on QoL in NPC survivors [19], and McDowell et al. found that post-treatment hearing loss and cranial neuropathies may predict a poorer QoL [37]. However, these studies only looked at the QoL up to five years after RT, and there is no literature on the QoL over a longer period. Moreover, previous studies found that health-related QoL in young and older adult patients differed for malignant tumours, such as haematological malignancies [38]. However, no studies have reported the long-term QoL for survivors of paediatric cancer or compared the QoL for survivors of paediatric and adult patients with NPC.
Survivors of paediatric cancer have better long-term QoL than adult. In this study, they had higher scores in PF, RF, and SF but worse CF scores than adult patients. Chen et al. found that paediatric patients achieved superior survival outcomes compared with adult patients in the era of IMRT [9]. In addition, it was reported that paediatric patients have less late toxicities [9, 19]. Chen et al. found that grades 3–4 dry mouth, dermal dystrophy, cervical fibrosis, and radiation encephalopathy were significantly lower in children than in adults [9]. Similarly, our study found that survivors of paediatric cancer had less insomnia, constipation, and diarrhoea than adults, which can affect their QoL.
Notably, survivors of paediatric cancer have worse CF outcomes than adult patients. This may be because over 90% of paediatric patients had T3–4 stage cancer when diagnosed; therefore, the temporal lobe of the brain and other vital organs in the head are vulnerable to radiation exposure during RT. The temporal lobe may be more sensitive to radiation in paediatric patients than in adults at the same doses; therefore, it is advisable to use precise target delineation in paediatric patients or adjust the radiation dose to the primary tumour [39, 40].
Furthermore, we found that QoL and CF in survivors of paediatric cancer were mainly correlated with staging at diagnosis. For example, survivors of paediatric cancer with early T1 stage disease had better QoL and CF outcomes than patients with T3 or T4 stage. This observation can be attributed to the reduced damage to the surrounding normal tissue due to smaller localized tumours in the early stages, resulting in a better QoL and CF outcomes after treatment. In contrast, the QoL and PF and RF of adult survivors were primarily associated with pre-treatment EBV DNA levels. We observed a significant relationship between adult SF and N stage. Patients with a more extensive N stage before treatment appeared to exhibit more noticeable lymph node swelling and a larger irradiated tumour area during RT. Since nasopharyngeal primaries are difficult to detect, the most common symptom of NPC at initial diagnosis is painless cervical lymphadenopathy. Patients with enlarged lymph nodes prior to treatment experience regression of their lymph nodes after treatment, and the observable therapeutic outcome motivates them to remove the social barriers associated with tumours. Yang et al. confirmed that patients’ SF consistently declined before treatment, during RT, and at the end of RT. However, the patients’ SF scores improved during the follow-up period and were even higher than before treatment (P = 0.016) [41].
For the first time, we confirmed different factors that influence long-term QoL for survivors of paediatric and adult patients, with pre-treatment T stage having the greatest impact on QoL for survivors of paediatric cancer and pre-treatment EBV DNA levels having the greatest impact on adult survivors. It is well known that a high EBV DNA load is representative of a high tumour burden, which is responsible for worse QoL after treatment [41, 42]. Our previous study found that pre-treatment EBV DNA load was significantly associated with QoL in patients aged 11–72 years. This finding differs in part from our results and may be due to the median age of our patients being 45 years, which resulted in only a small number of patients aged 11–21 years old being included in the paediatric group in our study [42]. It is possible that different results would have been obtained if those patients had been studied independently. We believe that the reason for the weak correlation between QoL in paediatric patients and pre-treatment EBV DNA load may be that the EBV DNA assay detects apoptotic and necrotic circulating tumour cells rather than all tumour cells that are present, and EBV may remain latent in childhood. In addition, according to Qiu et al., the pre-treatment EBV DNA level in children with NPC is not a reliable indicator of tumour burden, and they suggested an optimal cut-off value of 40,000 copies/ml for the pre-treatment EBV DNA load in children, which is significantly higher than the value of 4,000 copies/ml that we used [43]. At the same time, we observed that QoL was not associated with T stage, which aligns with our expectations: unlike EBV DNA, T stage primarily reflects the extent of local tumor invasion within the nasopharynx. Additionally, N stage plays a critical role in clinical practice. Up to 80% of patients with nasopharyngeal carcinoma present with cervical lymph node metastasis (N1-N3) as a primary symptom before treatment. Research indicates that patients with advanced N stages are more likely to develop extensive metastatic disease, making N stage a significant prognostic indicator [44, 45]. Therefore, in southern China, a region with a high incidence of nasopharyngeal carcinoma, EBV DNA can serve as a critical marker for integrating T and N stages in tumor evaluation [46].
Compared to previous studies investigating the QoL of paediatric or adult patients with NPC [8, 19, 33], our study has the following advantages. First, the sample size of paediatric patients with NPC was the largest in the field of QoL studies. Second, we used PSM to minimise differences in clinicopathological factors between adult and paediatric patients with NPC. Finally, for the first time, we compared the differences in the long-term QoL between paediatric and adult NPC survivors and found that paediatric and adult patients have different factors that affect their QoL. This will help healthcare professionals focus on the different clinical characteristics of paediatric and adult patients with NPC, tailor care for both age groups, and start interventions as early as possible to promote better long-term health outcomes.
This study has certain limitations. Conducted as a single-center investigation in a region with high prevalence in southern China, it may be subject to biases inherent in retrospective studies. Moreover, QOL data were collected at only one time point. Future research should be multi-center and include longitudinal QOL assessments at multiple time points to facilitate a more comprehensive evaluation of patient quality of life.
Conclusions
Survivors of paediatric cancer exhibit a superior QoL compared to their adult counterparts. Moreover, it is worth considering that pre-treatment factors may exert a significant influence on the QoL of survivors following treatment. These differences highlight the need to tailor care to both age groups to promote better long-term health outcomes.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Acknowledgements
We kindly thank the editor and reviewers for careful review and valuable comments, which have led to a significant improvement of the manuscript.
Abbreviations
- NPC
Nasopharyngeal carcinoma
- QoL
Quality of life
- EORTC QLQ-C30
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30
- EBV
Epstein–Barr virus
- AJCC
American Joint Committee on Cancer
- RT
Radiotherapy
- IMRT
Intensity-modulated radiotherapy
- PSM
Propensity score matching
- MRI
Magnetic resonance imaging
- PET-CT
Positron emission tomography/computed tomography
- SYSUCC
Sun Yat-sen University Cancer Centre
- PF
Physical functioning
- RF
Role functioning
- EF
Emotional functioning
- CF
Cognitive functioning
- SF
Social functioning
Author contributions
All authors contributed to the study conception and design. Study conception and design, supervision of the project, quality assessment, review, and approval of the manuscript: Qiu-Yan Chen, Hai-Qiang Mai and Lin-Quan Tang. Investigation, data curation, formal analysis and visualization: Jing Jin, Shan-Shan Guo, Li-Ting Liu. Data curation: Dong-Xiang Wen, Yu-Jing Liang, Xue-Song Sun, Jie-Yi Lin and Si-Qi Liu. Contributed to validation: Jing Jin, Dong-Xiang Wen, Rong-Ping Liu. Original draft writing: Jing Jin. Review and edit draft: Qiu-Yan Chen, Hai-Qiang Mai and Lin-Quan Tang. Final approval of manuscript: All authors.
Funding
This work was supported by the National Key Research and Development Program of China (2022YFC2705005, 2022YFC2505800), National Natural Science Foundation of China (No. 32200651, 82203776, 82203125, 82222050, 82272739, 82272882, 82173287, 82073003, 82003267, 82002852), Guangdong Major Project of Basic and Applied Basic Research (HRB103), Sun Yat-sen University Clinical Research 5010 Program (No. 201315, 2015021, 2017010, 2019023), Innovative Research Team of High-level Local Universities in Shanghai (SSMU-ZLCX20180500), Natural Science Foundation of Guangdong Province for Distinguished Young Scholar (No. 2018B030306001), Pearl River S&T Nova Program of Guangzhou (No. 201806010135), Planned Science and Technology Project of Guangdong Province (2019B020230002), and Fundamental Research Funds for the Central Universities.
Data availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Declarations
Ethical approval
This retrospective study was approved by the Clinical Research Committee of Sun Yat-sen University Cancer Centre.
Informed consent
Patients were required to provide written informed consent before enrolling in the study. Informed consent was obtained from parents and/or guardian for research participants under 16 years of age.
Consent for publication
No applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Jing Jin, Shan-Shan Guo, Li-Ting Liu and Dong-Xiang Wen (authors) contributed equally to this study.
Lin-Quan Tang, Hai-Qiang Mai and Qiu-Yan Chen (senior authors) contributed equally to this study.
Contributor Information
Lin-Quan Tang, Email: tanglq@sysucc.org.cn.
Hai-Qiang Mai, Email: maihq@sysucc.org.cn.
Qiu-Yan Chen, Email: chenqy@sysucc.org.cn.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.