Abstract
Objective
Many female patients with nasopharyngeal carcinoma (NPC) desire to reproduce after treatment. To evaluate the outcomes of subsequent pregnancy after NPC and explore the prognostic effects of pregnancy in women.
Methods
Female patients with locoregional NPC were included, and their pregnancy status, newborn information, and obstetric information were collected. Pregnant patients after therapy were matched to non-pregnant patients for survival analysis and overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRFS) were assessed.
Results
Of 895 patients, 79 conceived after NPC treatment. Of these, 52 women successfully delivered, and the rest had abortions. No abnormalities were recorded in any of the newborns and the caesarean section rate was 30.1%. The median birth weight of newborns was 3.11 kg. Patients who delivered successfully were younger than those who had an abortion. Among the pregnancies, four cases of spontaneous abortion and two cases of ectopic pregnancy were recorded. No significant differences in OS, DFS, LRFS, or DMFS were observed between the 79 subsequently pregnant patients and 315 matched non-pregnant patients.
Conclusion
Pregnancy after NPC treatment was not associated with adverse clinical outcomes. Abortion may not be a remedial choice post-treatment in patients with NPC.
Keywords: Nasopharyngeal carcinoma, pregnancy, reproduction, prognosis
Introduction
Nasopharyngeal carcinoma (NPC) is an endemic disease, of which 70% occurs in East and Southeast Asia [1,2]. The treatment strategies for nasopharyngeal carcinoma have undergone significant advancements in recent years, include radiotherapy (RT), chemotherapy, and immunotherapy. RT is the recommended primary treatment modality for patients with stage I-II NPC. However, more than 70% of the patients with NPC, were confirmed to have locoregionally advanced NPC at first diagnosis. For those patients, chemotherapy combined with radical RT have become the primary treatment modality, significantly enhancing treatment efficacy [3]. Particularly for complex cases, the role of multidisciplinary teams (MDT) has become increasingly important in developing personalized treatment plans [4]. MDT’s comprehensive management not only improves the precision of treatment but also addresses various issues patients may face during therapy. With the improvement in therapeutic patterns, the 5-year overall survival (OS) has greatly improved for patients with NPC [5,6]. With the increase in survival of these patients, more attention should be paid to post-treatment quality of life.
Approximately, 28% of patients with NPC are women [7]. As women have better clinical survival outcomes than men and patients aged <40 years have a higher survival rate than older patients [8], an increasing number of young female patients have long-term survival after treatment. Furthermore, young female patients with NPC may desire to reproduce after recovery. Previous studies have revealed that pregnancy may not affect clinical outcomes in different types of cancer. For breast cancer patients who are pregnant after completing treatment, studies have discovered that the risk of cancer recurrence, metastasis, or death does not increase in pregnant women [9–12]. Weibull et al. [13] reported that patients who were pregnant after Hodgkin’s lymphoma treatment had similar relapse rates to those who were not pregnant. Most patients with NPC experience recurrence and metastasis within three years [2]; however, whether pregnancy after treatment affects cancer recurrence or distant metastasis in patients with NPC remains unclear. Early studies have reported that relapse and mortality rates did not significantly increase in patients who were diagnosed with NPC during pregnancy [14,15]; however, for patients who conceived after NPC treatment, the prognostic impact of pregnancy is still inconclusive. Hence, the correlation between pregnancy after treatment and recurrence or distant metastasis in NPC patients should be explored.
Moreover, it is unclear whether antitumor treatments for cancer patients could increase the risk of adverse pregnancy outcomes. Clark et al. [16] and Armuand et al. [17] reported increased rates of delivery and obstetric complications in cancer survivors. Similarly, Dalberg et al. [18] revealed that the rates of low birth weight and deformity increased in women after breast cancer treatment. However, a meta-analysis concluded that chemotherapy does not increase adverse pregnancy outcomes [19]. Another study [20] has revealed that the risk of adverse birth outcomes was similar between breast cancer survivors and women without cancer. In the field of NPC, studies investigating the association between antitumor treatments and the risk of adverse pregnancy outcomes are scarce.
Therefore, this retrospective matched-control study aimed to explore the influence of NPC treatment on prognosis and fertility outcomes in female patients.
Patients and methods
Study design
First, we identified 1,052 female patients with newly diagnosed locoregional NPC between June 2007 and December 2015 at a reproductive age from the Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou (Figure 1). The inclusion criteria were as follows: (i) women aged between 15 and 40 years; (ii) pathological diagnosis with initial primary locoregional NPC and without metastasis within 1 year, (iii) histology shown to be nonkeratinizing carcinoma, according to the World Health Organization (WHO); and (iv) treated with chemoradiotherapy or RT alone at our institution. Subsequently, the included patients were divided into two groups: (i) pregnant group, patients who were pregnant after anti-tumor treatment for NPC, except those who developed disease progression before pregnancy; and (ii) non-pregnant group, patients who did not become pregnant after chemoradiotherapy.
Figure 1.
Flowchart depicting patient selection.
The Sun Yat-sen University Cancer Center Ethics Committee approved the study protocol (GZR2014-069). All patients who were involved provided written informed consent.
We manually matched the patients in the pregnant group with the best-matched patients in the non-pregnant group at a ratio of 1:4. We endeavored to match the following variables in decreasing order: nodal status, tumor size, Epstein–Barr virus (EBV) DNA copies, treatment strategy, radiation technique, and age at diagnosis. However, to include as many pregnant women as possible, we included three matched patients only if the fourth matched patient was not obtained after relaxing the matching criteria. Moreover, to avoid the impact of guaranteed time bias, the disease-free interval (DFI) for each non-pregnant patient was required to be no shorter than the time between NPC diagnosis and the conception date of the corresponding matched pregnant patient. DFI was defined as the interval from the date of NPC diagnosis to the date of local or distant relapse, secondary malignancy, and death from any cause.
In the subgroup analysis, for patients with more than one pregnancy after NPC, a pregnancy that resulted in a normal delivery or a premature delivery was selected as the pregnancy event; otherwise, the pregnancy closest to the date of the NPC diagnosis was selected.
Follow-up and statistical analysis
Patients were assessed every 3 months during the first year after NPC treatment and every 6 months after 1 year. Basic chemical profiling, nasopharyngoscopy, magnetic resonance imaging, or computed tomography (CT) of the head and neck, as well as imaging of the chest and abdomen, were performed as follow-up examinations. Patients were required to undergo CT of the chest or abdomen, bone scan, or 18 F-fluorodeoxyglucose positron emission tomography–CT when clinically indicated. For each female patient, pregnancy status (including pregnancy time, pregnancy initiation time, pregnancy complications, and cause of abortion), newborn information (including the baby’s sex and birth weight), and obstetrical information (including delivery time, delivery method, and obstetric complications) were collected through phone call by experienced interviewers.
OS was defined as the time between the first diagnosis of NPC and the date of either the patient’s death from any cause or the date of their most recent follow-up. Disease-free survival (DFS) was measured from the first day of diagnosis to the date of relapse, metastasis, secondary cancer, death from any cause, or last follow-up. The time interval from the date of diagnosis to any observation of locoregional recurrence, distant metastasis, or the date of the final follow-up was used to calculate the locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS) rates.
The chi-square or Fisher’s exact test was used to compare categorical variables between the groups, which were then reported as frequencies and percentages. The Wilcoxon test was used to compare continuous variables, which were expressed as medians and interquartile ranges (IQR). Kaplan–Meier curves and the log-rank test were used to compare the prognosis between the pregnant and non-pregnant groups. The hazard ratio (HR) and 95% confidence interval (CI) of the pregnant group compared to the non-pregnant group were estimated using the Cox regression model. Furthermore, we applied multivariate Cox regression analyses, which included the following factors: age, familial history, T stage, N stage, RT technique, pretreatment EBV DNA level, and pregnancy/non-pregnancy. Statistical significance was defined as a two-sided P-value <0.05, and all statistical analyses were conducted using R software (version 4.0.2).
Results
Clinical characteristics of the study cohort
Overall, 1,052 patients were enrolled in our study, and 157 patients were excluded because of the loss of pregnancy or treatment information (Figure 1). Altogether, 94 (10.5%) of 895 patients became pregnant after NPC treatment, and we included 79 patients in the pregnant group after excluding patients due to lack of follow-up, missing date of conception, relapse before the date of pregnancy, and pregnancy at diagnosis. The median age of patients when they had their first child was 34 years (IQR, 30.0 to 36.5 years) in the pregnant group. The median time from NPC diagnosis to pregnancy was 46 months (IQR, 32.0 to 57.0 months). The peak time of progression in the original set (n = 1052) was 1–3 years after the NPC diagnosis. Among them, 137 cases demonstrated disease events during the follow-up period: 38 (27.7%) at 1 year, 47 (34.3%) at 1–2 years, and 23 (19.7%) at 2–3 years (Figure 2).
Figure 2.
The number of disease events (n = 216) and subsequent pregnancy (n = 79) for female patients with NPC diagnosed from 2007 to 2015, aged 18 to 40 years at diagnosis, metastasis-free at baseline.
A total of 315 non-pregnant patients were matched to 79 pregnant patients. Patient features are summarized in Table 1. Comparable clinical variables were observed between the pregnant and matched non-pregnant groups.
Table 1.
Baseline characteristics.
| Pregnancy group (n = 79) | Non-pregnancy group (n = 315) | P value | |
|---|---|---|---|
| Age at cancer diagnosis | 0.151 | ||
| ≤31 years, n% | 48 (60.8) | 163 (51.7) | |
| >31 years, n% | 31 (39.2) | 152 (48.3) | |
| Follow-up time (months) | 86 (65–101) | 73 (58-96) | 0.936 |
| NPC family history (n%) | 10 (12.7) | 28 (8.9) | 0.310 |
| Other malignancy family history (n%) | 8 (10.1) | 43 (13.7) | 0.404 |
| T stage (n%) | 0.894 | ||
| T1 | 6 (7.6) | 18 (5.7) | |
| T2 | 23 (29.1) | 90 (28.6) | |
| T3 | 37 (46.8) | 157 (49.8) | |
| T4 | 13 (16.5) | 50 (15.9) | |
| N stage (n%) | 0.866 | ||
| N0 | 9 (11.4) | 27 (8.6) | |
| N1 | 29 (36.7) | 126 (40.0 | |
| N2 | 30 (38.0) | 118 (37.5) | |
| N3 | 11 (13.9) | 44 (14.0) | |
| Overall stage (n%) | 1.000 | ||
| I or II | 17 (21.5) | 67 (21.3) | |
| III | 40 (50.6) | 160 (50.7) | |
| IVa | 11 (13.9) | 44 (14.0) | |
| IVb | 11 (13.9) | 44 (14.0) | |
| EBV (n%) | 0.983 | ||
| ≦1500 | 34 (43) | 136 (43.2) | |
| >1500 | 45 (57) | 179 (56.8) | |
| RT technique (n %) | 0.601 | ||
| 2D-CRT/3D-CRT | 20 (25.3) | 71 (22.5) | |
| IMRT | 59 (74.7) | 244 (77.5) | |
| Chemotherapy (n %) | 0.777 | ||
| RT only | 2 (2.5) | 16 (5.1) | |
| CCRT | 29 (36.7) | 115 (36.5) | |
| NART | 13 (16.5) | 50 (15.9) | |
| NART+CCRT | 35 (44.3) | 128 (40.6) | |
| Other chemotherapy | 0 | 6 (1.9) |
RT: radiotherapy; CCRT: concurrent therapy; NART: neoadjuvant therapy; 2D-CRT: two-dimensional conventional radiotherapy; 3D-CRT: three-dimensional conventional radiotherapy; IMRT: intensity-modulated radiotherapy; EBV: Epstein–Barr virus. 7th American Joint Commission on Cancer Staging System.
Pregnancy patterns, birth outcomes, and complication for female patients
In total, 95 subsequent pregnancies occurred in 79 women, and 12 (15.2%) had two or more pregnancies. Of the patients, 52 (65.8%) had at least one successful delivery (Table 2) and among the pregnancies, 3 cases of spontaneous abortion (3.2%) and one case of ectopic pregnancy were recorded. Twenty-seven (34.2%) female patients had abortions; among them, one case of spontaneous abortion and one case of ectopic pregnancy were recorded. Of the 25 women with induced abortions, 13 were concerned about tumor progression, four were worried about the child getting affected, and the rest were mainly concerned with other personal reasons. Those who successfully delivered were younger than those who had an abortion (median age, 29 years vs. 32 years; p < 0.001). They were also likely to have conceived for more than 3 years after NPC treatment (81.2% vs. 37%, p < 0.001). More nulliparas were observed in those who delivered successfully (60.4% vs. 7.4%, p < 0.001).
Table 2.
Baseline data of successful delivery group and abortion group.
| Successful delivery (n = 52) |
Abortion (n = 27) |
P value | ||
|---|---|---|---|---|
| Age at cancer diagnosis | 29 (26–33) | 32 (29–33.5) | 0.013 | |
| <31 years, n% | 35 (67.3) | 13 (48.1) | 0.158 | |
| >31 years, n% | 17 (32.7) | 14 (51.9) | ||
| Age at pregnancy | 0.172 | |||
| <31 years, n% | 21 (40.4) | 6 (22.2) | ||
| >31 years, n% | 31 (59.6) | 21 (77.8) | ||
| Time intervals between pregnancy and diagnosis | 48.5 (40.5–60) | 32 (24–47) | <0.001 | |
| <36 months, n% | 43 (82.7) | 10 (37.0) | <0.001 | |
| >36 months, n% | 9 (17.3) | 17 (63.0) | ||
| Overall stage (n %) | 0.652 | |||
| II | 9 (17.3) | 8 (29.6) | ||
| III | 28 (53.8) | 12 (44.4) | ||
| IVa | 7 (13.5) | 4 (14.8) | ||
| IVb | 8 (15.4) | 3 (11.1) | ||
| EBV (n %) | 0.048 | |||
| ≦1500 | 27 (51.9) | 7 (25.9) | ||
| >1500 | 25 (48.1) | 20 (74.1) | ||
| RT technique (n%) | 0.146 | |||
| 2D-CRT | 10 (19.2) | 10 (37.0) | ||
| IMRT | 42 (80.8) | 17 (63.0) | ||
| Chemotherapy (n %) | 0.977 | |||
| RT only | 2 (3.8) | 0 (0.0) | ||
| CCRT | 19 (36.5) | 10 (37.0) | ||
| NART | 8 (15.4) | 5 (18.5) | ||
| NART+CCRT | 23 (44.2) | 12 (44.4) | ||
| Nullipara (n %) | <0.001 | |||
| Yes | 29 (55.8) | 2 (7.4) | ||
| No | 23 (44.2) | 25 (92.6) | ||
RT: radiotherapy; CCRT: concurrent therapy; NART: neoadjuvant therapy; 2D-CRT: two-dimensional conventional radiotherapy; 3D-CRT: three-dimensional conventional radiotherapy; IMRT: intensity-modulated radiotherapy; EBV: Epstein–Barr virus. 7th American Joint Commission on Cancer Staging System. The bold values are statistically significant at p < 0.05.
Of the 53 deliveries, a caesarean section was performed in 16 (30.1%). The median birth weight was 3.11 kg (range, 1.80–3.75 kg). Two births occurred before 37 weeks: one at 32 weeks (weighed 1.8 kg, appropriate for gestational age) and the other at 35 weeks (weighed 2.0 kg, small for gestational age).
All the children were alive without retardation or deformity at the last follow-up. Moreover, we did not observe any maternal complications (gestational diabetes mellitus, preeclampsia, preterm delivery, or postpartum hemorrhage) or perinatal events (placental abruption or placenta previa).
Relationship between pregnancy and prognosis of all the included patients
The median follow-up time for the pregnant and non-pregnant groups was 86 (range, 65–101) and 73 (range, 58–96) months, respectively. Two (2.5%) patients in the pregnant group had locoregional relapse, one (1.3%) had distant metastasis, and two (2.5%) had a second malignancy tumor (gastric cancer and thyroid cancer). Meanwhile, 19 (6%) patients in the non-pregnant group experienced locoregional relapse, 15 (4.9%) had distant metastasis, and 10 (3.5%) died. There was no statistically significant difference between the two groups in terms of DFS (5-year DFS rate: 94.7% vs. 90.9%, p = 0.12; Figure 3(B)). Similarly, we did not identify any differences in LRFS (p = 0.18; Figure 3(C)) or DMFS (p = 0.15; Figure 3(D)). A marginal difference in OS was observed between the two groups (p = 0.086, Figure 3(A)).
Figure 3.
Kaplan–Meier survival curves of OS (a), DFS (B), LRFS (C) and DMFS (D) for the subsequent group and the matched non-pregnant group.
Subgroup analysis for prognosis of different pregnancy outcomes
For further investigation, according to different pregnancy outcomes, the pregnant patients were divided into two subgroups: women who had completed their pregnancy and delivered their babies preterm or term (successful delivery group) and those who had a spontaneous or induced abortion (abortion group). The 5-year DFS rates of the 52 women in the successful delivery group and 27 in the abortion group were 94.0% and 83.9%, respectively (Table 2).
We found no significant differences in DFS (p = 0.72), DMFS (p = 0.62), or LRFS (p = 0.62) between the two subgroups. Compared with the corresponding matched non-pregnant group, the Cox regression results showed that the successful delivery group had no significant difference in DFS (HR = 0.629; 95%CI, 0.181–2.1833; p = 0.465; Figure 4). When comparing the abortion group with the corresponding matched non-pregnant group, similar results were observed for DFS (HR = 0.338; 95%CI, 0.078–1.463; p = 0.147).
Figure 4.
Forest plots of predefined subgroup analyses.
Subgroup analysis for prognosis of different times to pregnancy
Regarding the time to pregnancy after NPC diagnosis, patients who were pregnant were separated into two subgroups: patients who were pregnant within the first 3 years after the date of NPC diagnosis (early pregnancy group) and patients who were pregnant 3 years after the date of NPC diagnosis (late pregnancy group). Patient characteristics were not significantly different between the 26 women in the early pregnancy group and 53 women in the late pregnancy group (Table S1).
No significant differences in DFS (5-year DFS rate: 92.1% vs. 95.9%, p = 0.71), DMFS (p = 0.15), or LRFS (p = 0.60) were observed between the two subgroups. The DFS between patients in the late-pregnancy group and those in the corresponding matched non-pregnant group was comparable (HR = 1.092; 95% CI, 0.295–4.037; p = 0.895; Figure 4). However, a borderline P-value (HR = 0.259; 95% CI, 0.060–1.116; p = 0.070; Figure 4) for DFS was observed between patients in the early pregnancy group and those in the corresponding matched non-pregnant group. In order to assess whether a protective effect of early pregnancy was shown or whether the outcomes were confusing because those with a longer DFI had a greater chance of being matched with the late-pregnant group, we conducted a similar analysis between the two non-pregnant groups who were matched to the early and late-pregnant survivors. The non-pregnant group, which was matched to the early pregnancy subgroup, had significantly lower DFS (p < 0.001). Overall, these analyses suggested that the borderline P-value could have been influenced by selection bias.
Discussion
To our knowledge, this is the first relatively large-scale study to evaluate maternal and fetal outcomes as well as the prognostic effect of pregnancy in patients after NPC treatment. Pregnancy outcomes in this study were acceptable. Only four spontaneous miscarriages and two preterm births were reported among 95 pregnancies. Moreover, we discovered that subsequent pregnancy after locoregional NPC diagnosis did not decrease survival rate.
This finding is consistent with that of a Taiwanese study [21], which concluded that compared to pregnant women without a history of NPC, those with a history of NPC did not have significant high-risk obstetric events. Moreover, no greater risk of deformity or cancer was observed in the offspring of the cancer survivors. However, birth outcomes among survivors of NPC are less frequently reported, although some studies on childhood or adolescent cancers have reported adverse results. Danish et al. [22] also reported that cancer survivors do not have an increased risk of chromosomal abnormalities in their offspring compared with the offspring of their siblings. Meanwhile, a study which included 1264 children or adolescents who gave birth after tumor treatment revealed that the risk of preterm birth was higher than that of their siblings [23]. Another study [24] from Canada including 4062 survivors of childhood or adolescent cancer, shows similar adverse fertility outcomes. However, most of the women in the studies mentioned have leukemia and may require more extensive chemotherapy at a younger age compared to NPC patients. In a study of births among AYA cancer survivors diagnosed in the United States, Anderson et al. [25] reported similar increases in preterm birth and low birth weight compared to women without a history of cancer. Regarding Hodgkin lymphoma survivors, a study [26] involving 99 survivors who became pregnant after treatment, along with a meta-analysis [27], reported that adverse pregnancy outcomes did not increase among these survivors. Our findings indicate relatively fewer adverse outcomes in NPC survivors. Nevertheless, further research with larger sample sizes is needed to validate these findings. In summary, although we believe that women with a history of NPC after early adolescence are safe, it is still necessary to consider pregnancy after NPC treatment as a high-risk pregnancy. Women with NPC who have fertility concerns should initiate consultations on fertility preservation strategies immediately after diagnosis, and once pregnant, fetal development should be closely monitored.
Our study found that subsequent pregnancies after NPC treatment did not elevate the risk of adverse prognoses. Besides, we observed a similar prognosis between the abortion and matched nonpregnant groups. Studies conducted in Korea report that pregnancy following breast cancer does not negatively impact prognosis [12, 28]. Azim et al. [9] reported that pregnancy resulted in no adverse DFS after treatment for breast cancer, regardless of successful delivery or abortion. Similarly, after a long-term follow-up of breast cancer survivors, Lambertini et al. [10] did not identify a difference in prognosis between pregnant patients with or without miscarriage and non-pregnant patients. Besides, pregnancy after the diagnosis of thyroid cancer does not lead to disease progression [29, 30]. Moreover, another Swedish study reports that pregnancy in Hodgkin lymphoma survivors does not increase the relapse rate. Although research on NPC remains limited, findings from studies on other tumors are consistent with our conclusion that pregnancy following NPC treatment has a minimal impact on prognosis, thereby providing indirect support for our results. Hence, concerns about adverse prognoses related to pregnancy after NPC treatment may not be necessary and abortion due to fear of tumor progression is not recommended.
Furthermore, appropriate time for pregnancy is an important survivorship issue. In this study, we observed a trend toward higher DFS in the early pregnancy group. Our results are consistent with those for women after breast cancer of Azim et al. [9] and Matteo Lambertini et al. [10], which may have also demonstrated a protective effect in early pregnancy within the first 2 years. This may be due to the matching method (match by DFI ≥ time to pregnancy in matched pregnant patients). The patients with a relatively short DFI tended to match those in the early pregnancy group. Overall, time was not an independent factor influencing the prognosis of patients.
In general, although the time to conceive does not adversely affect prognosis, women are recommended to delay pregnancy after at least 6 months [31–33]. This is mainly beneficial for patients to recover from the functional damage caused by chemotherapy and allows patients to retain time for further treatment for early progression [34]. As for Hodgkin’s lymphoma, after the follow-up of 449 young female patients, Weibull et al. [13] advised women to wait 2 years for subsequent pregnancy due to the highest risk of relapse in the first 2 to 3 years after diagnosis. Generally, breast cancer survivors were recommended to postpone pregnancy for 2 years to allow the resumption of adequate ovarian function [35]. Pregnancy should be postponed for five years in patients with breast cancer who have a high risk of relapse [36]. There is no universally defined optimal time for patients to become pregnant after treatment of NPC. The decision should be based on several factors, including age, the risk of relapse, the completion of therapy, and ovarian function. Here, we found that the highest risk of progression occurred in the first three years. Thus, waiting for 3 years after diagnosis, if possible, is perhaps a suitable choice for those who want a subsequent pregnancy.
Advanced age is a risk factor for pregnancy complications, including pregnancy loss, stillbirth, foetal abnormalities, female infertility and obstetric complications [14, 37–41]. Notably, radiotherapy of the head and neck may cause gonadotropin deficiency via the hypothalamic–pituitary–ovarian axis, and gonadal toxicity, especially cisplatin-based chemotherapy, may increase the risk of premature menopause and ovarian failure, all of which may cause involuntary childlessness [21, 34, 42]. Hence, older patients need to weigh the advantages and disadvantages of delaying their pregnancy.
The 5-year DFS rates of the subsequent pregnant patients and the matched non-pregnant patients were 94.7% and 90.9% in this study, respectively, while a PFS rate of 74% in non-pregnant women was reported by Yi-Kan et al. [14] and 77% in patients with NPC was reported by Guo et al. [43]. It is reported that the NPC patients’ 5-year PFS rates for stages I, II, III, IVa, and IVb in a large cohort study by Sun et al. were 97.1%, 90.6%, 82.1%, 73.0%, and 65.4%, respectively [6]. The following factors may account for the relatively better survival of the patients in our study. First, our study included only female patients without metastasis who were aged ≤40 years [44–46]. Second, because of the matching method with DFI, patients with early disease progression were likely to be ruled out.
Our study has some limitations. First, although a matching method was used, we could not completely rule out selection bias in this retrospective study. Second, this was a single-center matched cohort study, although it was impossible to address the impact of subsequent pregnancy on patients after NPC treatment in a prospective randomized controlled study. Therefore, further validation will require data from a larger, well-conducted, multicenter, and retrospective study. Third, information on assisted reproductive technology (ART) was not available in this study.
Conclusions
Overall, pregnancy may not adversely affect the prognosis of patients with a history of NPC. Abortion was not suggested as a remedial choice because it did not result in a significant difference in survival rates. Delaying pregnancy for three years was recommended for these women. Despite acceptable pregnancy outcomes, conception in women after NPC treatment should be regarded as potentially high-risk and continuously monitored.
Supplementary Material
Acknowledgments
The authors would like to thank all women who participated in this study.
Funding Statement
The grants supporting this research were as follows: the National Natural Science Foundation of China (No. 81602371 and No. 81672868), the National Key R&D Program of China (2017YFC1309003 and 2017YFC0908500), the Sun Yat-sen University Clinical Research 5010 Program, the Natural Science Foundation of Guangdong Province (No. 2017A030312003), the Planned Science and Technology Project of Guangdong Province (2019B020230002), and the Health & Medical Collaborative Innovation Project of Guangzhou City (No. 201803040003).
Author contributions
Study concepts and design: Haiqiang Mai, Qiuyan Chen, and Shanshan Guo; data acquisition: Meijuan Luo, Liting Liu, Zhenchong Yang; data analysis: Yujing Liang and Dongxiang Wen; statistical analysis: Sailan Liu and Xiaoyun Li; manuscript editing: Meijuan Luo, Liting Liu, and Zhenchong Yang; manuscript review: Haiqiang Mai, Chuanmiao Xie, Linquan Tang, Qiuyan Chen, and Shanshan Guo.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Data availability statement
The data that support the findings of this study are available from the corresponding author, H.M., upon reasonable request.
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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 data that support the findings of this study are available from the corresponding author, H.M., upon reasonable request.