Gemcitabine and cisplatin induction chemotherapy followed by concurrent chemoradiotherapy for stage III–IVA nasopharyngeal carcinoma: A real-world study

Abstract

Introduction:

This study aims to evaluate the efficacy of combining induction chemotherapy with concurrent chemoradiotherapy for patients with stage III–IVA nasopharyngeal carcinoma (NPC), particularly focusing on cases associated with Epstein–Barr virus infection. The primary focus is on treatment response and disease control.

Methods:

This retrospective cohort study analyzed data from 81 patients with stage III–IVA NPC (excluding T3N0M0) treated with gemcitabine and cisplatin as induction chemotherapy, followed by concurrent chemoradiotherapy at the Vietnam National Cancer Hospital. Patient data and follow-up information were collected between June 2021 and June 2024, focusing on disease-free survival (DFS) as the primary outcome and secondary outcomes including factors affecting DFS and treatment-related toxicity.

Results:

In the initial 3-month period, 76 out of 81 patients achieved a complete response, and five patients achieved a partial response. The follow-up period averaged 18.7 ± 5.3 months, with a 2-year DFS rate of 77.6%. Key factors influencing DFS included patient age, N stage, disease stage, and treatment interruptions. Grade 3 toxicities observed included neutropenia (17.3%) and mucositis (32.1%), while grade 4 toxicity was limited to nausea (2.4%). Additionally, 2.6% of patients experienced delayed grade I–II toxicities, with some presenting grade III anorexia.

Conclusion:

Our findings suggest that gemcitabine and cisplatin induction chemotherapy, followed by chemoradiotherapy, may result in a high response rate and effective disease control with manageable toxicity. However, further research is needed to evaluate long-term outcomes and potential delayed adverse effects to confirm these initial observations.

Keywords

Nasopharyngeal carcinoma (NPC)chemoradiotherapy Vietnam National Cancer Hospital induction chemotherapy disease-free survival

Introduction

Nasopharyngeal carcinoma (NPC) is a prevalent disease that is primarily seen in Southeast Asia, East Asia, and North Africa due to its geographic dispersion.¹ Based on the data from GLOBOCAN 2022, NPC ranks as the 23rd most prevalent cancer globally, with a staggering number of over 130,000 newly diagnosed cases. Additionally, it holds the 22nd position in terms of mortality rate, which is at 8%.¹ In Vietnam, NPC is ranked 9th in incidence with over 6000 new cases and 7th in mortality rate with a rate of 3%.²

The typical symptoms include a headache, tinnitus, and nasal congestion. The majority of cases are in the advanced stages (III, IV), comprising more than 80% of the total.³

The Phase III Randomized Intergroup Study 0099 demonstrated that concurrent chemoradiotherapy (CRT) is the established treatment for locoregionally progressed NPC (stages II–IVB) and is endorsed by NCCN as the preferred approach for these NPC stages.⁴ Recent clinical trials have demonstrated the role of induction chemotherapy plus CRT in stage III–IVB NPC.^5–11 Two multicenter randomized controlled trials conducted in China utilized two different induction regimens: gemcitabine plus cisplatin, and docetaxel plus cisplatin plus 5-fluorouracil.¹² In both studies, these regimens were followed by CRT. Compared to CRT alone, the induction plus concurrent chemoradiotherapy regimens were found to be inferior in overall survival (OS) but non-inferior in terms of toxicity effects.^6,9 The NCCN currently classifies these two treatment plans as IA guidelines for managing Epstein–Barr virus (EBV)-related locoregional NPC.

In Vietnam, gemcitabine and cisplatin induction chemotherapy has been widely adopted for stage III–IVA (excluding T3N0M0) NPC patients since 2019. However, studies assessing the treatment response and adverse effects of this regimen are still lacking. Thus, our study aims to provide real-world data on treatment response and adverse effects, particularly on the cumulative dose and tolerability of cisplatin in CRT.

Materials and methods

Methods

Study design and data sources

This retrospective cohort study utilized patient data collected from medical records and follow-up information at the Vietnam National Cancer Hospital from June 2021 to June 2024. Convenience sampling was employed, including all eligible patients treated at the hospital who met study criteria within this timeframe. A total of 81 patients were included in the analysis.

Eligibility criteria

Eligible patients met the following criteria:

Diagnosis of NPC confirmed via pathology;

Classification as stage III or IVA according to the American Joint Committee on Cancer (AJCC) 8th edition;

Treatment with gemcitabine and cisplatin induction chemotherapy followed by concurrent chemoradiotherapy (CCRT);

An Eastern Cooperative Oncology Group (ECOG) performance status score of 0–1; and

Availability of comprehensive patient data for analysis.

Exclusion criteria

Patients were excluded if they had any of the following:

Stage T3N0M0;

Secondary malignancies;

Chronic disorders, such as heart failure or renal failure;

Prior treatment of the nasopharyngeal and/or neck region with radiotherapy, chemotherapy, or surgery; and

Pregnancy.

Ethical approval

The study was approved by the Ethics Committee in Biomedical Research at Hanoi Medical University (IRB—VN01001; IRB00003121) under approval number 1469/GCN-HMUIRB, granted on 12 April 2024. Due to the retrospective nature of the study, written informed consent could not be obtained as patients had already completed treatment. However, oral informed consent was documented in each patient's medical record at the Vietnam National Cancer Hospital in accordance with the Institutional Review Board's ethical guidelines. All procedures involving human participants followed the ethical standards of the institutional and national research committees and the 1975 Declaration of Helsinki, revised in 2013. Reporting adheres to the STROBE guidelines. To protect patient privacy, all patient details have been fully de-identified to prevent any potential identification of individual participants.

Treatment protocol

All patients followed a standardized treatment protocol at the Vietnam National Cancer Hospital. For detailed specifics on chemotherapy and radiotherapy procedures, dose adjustments, and management of adverse effects, please refer to the Appendix.

Outcome assessment

Treatment response was evaluated using clinical examinations and blood tests every 3 weeks, supplemented with imaging studies (MRI, CT, PET-CT) as necessary, according to RECIST 1.1 criteria. Adverse effects were recorded before each treatment cycle and graded following NCI Common Terminology Criteria for Adverse Events (CTCAE) version 2.0.

Study endpoints

The primary endpoint was disease-free survival (DFS), defined as the time after initial cancer therapy during which a patient remains alive without any signs or symptoms of the cancer. Secondary endpoints included variables affecting DFS, such as demographic and clinical factors, and adverse effects observed during treatment.

Statistical analysis

Data analysis was performed using SPSS version 20.0. Descriptive statistics were used to summarize patient demographics and clinical characteristics. For survival analysis, the Kaplan–Meier method was applied to estimate DFS and OS, with comparisons between groups conducted using the Log-rank test. A significance level of p < 0.05 was considered statistically significant. Given the sample size of 81 patients, statistical methods were selected to balance the limited sample with the need for reliable, interpretable survival outcomes, emphasizing proportional hazard assumptions for Log-rank test validity.

Results

Patients characteristics and treatment details

From June 2021 to June 2024, a total of 81 patients meeting the selection criteria were identified at the Vietnam National Cancer Hospital. Their characteristics are presented in Table S1. The mean age was 52.14 ± 11.92 years, with a male-to-female ratio of 2.6:1. The most frequently reported chief complaints were tinnitus (64.2%) and cervical lymphadenopathy (64.2%). Notably, 76.5% of lymph node groups were found on both sides of the neck, with level II accounting for 96.3% and level VII for 72.8%.

Among the 81 patients who completed three cycles of induction chemotherapy, 78 patients (96.3%) received CRT with at least two cycles of cisplatin. The total cumulative dose of cisplatin during CRT for each patient reached ≥ 200 mg/m², with 62 patients (76.5%) completing all three cycles. Only three patients (3.7%) received one cycle due to grade III and IV toxicities that were unresponsive after two weeks of supportive treatment. All patients were treated with a total radiation dose of 70 Gy to the primary tumor and metastatic lymph nodes.

In terms of treatment tolerance, 66/81 patients (81.5%) experienced interruptions during the radiotherapy process. The primary causes of these interruptions were side effects from radiotherapy (39/66 patients, 59.1%), primarily oral mucositis and skin dermatitis. The average duration of treatment interruptions was 16.12 ± 10.6 days. Such interruptions impacted the overall time to complete the radiotherapy regimen, with a mean duration of 61.12 ± 10.6 days for the entire treatment course. These factors indicate that the tolerability of treatment among patients can be further improved through effective management of adverse effects.

Finally, in our study, 67/81 (82.7%) patients were treated using intensity-modulated radiation therapy (IMRT) or volumetric modulated arc therapy, while 14/81 (17.3%) patients received three-dimensional conformal radiation therapy (3D-CRT). Numerous studies have demonstrated that IMRT reduces unwanted side effects compared to 3D-CRT, thereby enhancing patient adherence to treatment and improving long-term quality of life.

Response

A total of 4.9% of patients (4 patients) experienced a complete response (CR), 88.9% (72 patients) had a partial response (PR), and 6.2% (5 patients) had stable disease after three cycles of induction chemotherapy. After three months of completing CRT, the rates of CR and PR were 93.8% and 6.2%, respectively (Figure S1), with no patients exhibiting stable disease, disease progression, metastasis, or mortality during the treatment. The McNemar test revealed a statistically significant difference between the 1-month response rate and the 3-month response rate (p < 0.0001). Among the PR group, there was one patient who had residual tumor and lymph nodes affected. Additionally, two patients with inoperable remaining tumors were treated with adjuvant chemotherapy, while two patients with remaining lymph nodes underwent selective cervical lymphadenectomy and were closely monitored afterwards.

At the conclusion of the trial, 95.1% of the patients (77 out of 81) were still living, while the remaining four patients (4.9%) had died, all due to recurrence or distant metastasis. The rate of recurrence was 14.5%, whereas the rate of metastasis was 9.9%. Among recurrence cases, the most frequent location of recurrence was at the primary tumor site (45.4%). Among metastasis cases, the liver (57.1%) and lungs (28.6%) were the most common sites. The mean duration until recurrence was 11.2 ± 5.5 months, whereas the mean duration until metastasis was 11.9 ± 4.3 months (Table S2).

OS

The median follow-up time was 26 months (standard deviation, 3.56). At the conclusion of the study, 77 patients were alive, while four patients (5.2%) had died, all due to disease-related causes: three from metastases to the liver and lungs, and one from local recurrence leading to hemorrhage. The OS rate at 2 years was 96.1% (Figure S2). These findings underscore the effectiveness of the treatment protocol in prolonging survival in patients with advanced NPC.

DFS

After completing chemoradiotherapy, a cohort of 76 patients who had a CR were monitored to assess their DFS. The mean follow-up duration was 18.7 ± 5.3 months, ranging from 5 to 29 months (Figure S3). The one-year and two-year DFS rates were 86.8% and 77.6%, respectively.

Prolonging the completion of chemoradiotherapy by more than 7 days showed an adverse effect on DFS as compared to individuals who had a delay of 7 days or less (Figure S4). The observed difference was statistically significant, as indicated by a p-value of 0.023 (p < 0.05). Likewise, age is a contributing element that impacts DFS. Patients aged 51 and above exhibited a reduced DFS rate compared to those below the age of 51, with a statistically significant difference (p = 0.018, p < 0.05) (Figure S4).

Lymph node stage and disease stage are two factors affecting DFS, with statistically significant differences observed through univariate analysis using the Log-rank test, with p-values of 0.046 (p < 0.05) and 0.031 (p < 0.05), respectively (Table S3).

Toxicity

Most patients experienced grade I and II acute toxicities, with an increase in grade III and IV toxicities primarily during the concurrent chemoradiotherapy phase (Table S4). Common toxicities included neutropenia (17.3%), mucositis (32.1%), and nausea (11.1%). Among these, three patients required discontinuation of platinum after completing two cycles due to severe grade III and IV toxicities that persisted despite two weeks of supportive care. These patients continued with radiotherapy alone. No toxicity-related fatalities occurred during the treatment.

Following a mean follow-up of 18.75 ± 5.3 months, persistent grade III xerostomia was observed in only two patients (2.6%), while 64.9% experienced grade I and II xerostomia. Grade I and II trismus and neck stiffness were observed in 7.8% and 11.7% of patients, respectively. Additionally, 27.3% of patients developed grade I and II hearing impairment (Table S4).

Discussion

Due to notable advancements in local disease management through the use of IMRT, distant metastasis frequently emerges as the predominant form of treatment failure.^13,14 Two recent trials have demonstrated that the use of induction chemotherapy combined with CRT utilizing the IMRT approach is effective in treating locally advanced nasopharyngeal cancer (NPC).^6,10 Since 2019, the use of gemcitabine and cisplatin as induction chemotherapy has been recommended (category IA) for patients with EBV-related locally progressed NPC. However, there is currently insufficient data regarding the effectiveness and side effects of this treatment regimen in clinical practice. Therefore, we conducted this study to complement the current data.

The high rate of CR observed at three months suggests an ongoing therapeutic effect following radiation in advanced NPC, supporting the importance of delayed assessment for more accurate outcome evaluation. Variability in complete response rates across studies may be attributed to differences in cohort characteristics; our patients predominantly had advanced-stage disease with extensive tumor involvement, particularly in lymph nodes. Which likely contributed to our lower complete response rate relative to studies by Zhang and Yan Wang, which included more cases with less advanced disease.^10,15 Moreover, treatment delays due to COVID-19 disruptions, adverse effects, and facility maintenance highlight the need for uninterrupted therapy to achieve optimal outcomes in advanced-stage NPC cases.

The COVID-19 pandemic posed significant challenges to the management of NPC, affecting treatment timelines and protocols. Restrictions led to delays in radiotherapy and chemotherapy, which are essential in advanced NPC treatment, potentially lowering the rates of local control and increasing risks of recurrence and distant metastasis.¹⁶ Such disruptions disproportionately affect patients with advanced NPC, where timely and continuous therapy is crucial for optimal outcomes.¹⁷

During the pandemic, patient access to healthcare was limited because of mobility restrictions and the reallocation of healthcare resources. This hindered side effect management and compromised treatment adherence, which may explain the variations in complete response rates observed during this period.¹⁷ These findings highlight the need for resilient treatment strategies in oncology to mitigate the impact of future public health emergencies.

Our study demonstrated a two-year OS rate of 96.1% with a median follow-up time of 26 months, underscoring the effectiveness of the gemcitabine and cisplatin regimen in combination with CRT in prolonging survival among patients with stage III–IVA NPC (Figure S2). These results align with previous findings on the benefits of induction chemotherapy and CRT in enhancing survival for patients with locoregionally advanced NPC. Studies by Zhang et al.⁶ and Wang et al.¹⁰ have shown that, although NPC is often diagnosed at an advanced locoregional stage, it generally responds well to treatment due to its high radiosensitivity, while chemotherapy provides early control of potential distant metastases.

While the OS outcomes in our study are promising, the relatively short follow-up period (26 months) might be insufficient to capture all mortality events, especially in NPC, which typically has a relatively long prognosis. This represents a limitation in OS analysis, potentially underrepresenting the long-term efficacy of this regimen. Additionally, five patients who achieved PR at three months received salvage therapy with maintenance chemotherapy or selective neck dissection, which might impact OS results and introduce bias. Future studies with extended follow-up periods and the exclusion or control of post-treatment interventions will enable more accurate assessments of the regimen's long-term survival benefits.

Among the 81 patients enrolled in this trial, five individuals who showed a PR 3 months after therapy were not considered in the evaluation of DFS. The mean duration of follow-up for the 76 patients included in the assessment of DFS was 18.7 ± 5.3 months, and the DFS rate at 2 years was 77.6% (Figure S3).

Multiple studies indicate that the mean duration between the initiation of therapy and the reappearance of symptoms ranges from 1 month to 10 years. The rates of recurrence are most elevated within the initial 2–3 years following the completion of treatment and progressively diminish after a span of 5 years.^15,18 Regular and thorough monitoring after the initial therapy can aid in promptly identifying any signs of recurrence.

Our study demonstrated inferior disease-free survival outcomes in comparison with most previous trials. A study by Yang et al.¹⁹ indicated that after an average follow-up period of 82.6 months, the 5-year DFS rate was 73.4% in the IC + CCRT group and 63.1% in the CCRT alone group (p = 0.007). In a study by Peng et al.,²⁰ after a median follow-up of 57.13 months, the OS rate and the 5-year DFS rate were 87.2% and 80.7%, respectively. The disparity can be elucidated by the fact that a considerable number of patients in our study were in an advanced stage, had considerable delays in receiving radiotherapy, and had a higher average age compared with those in other trials. These factors collectively led to considerably poorer treatment results. In the investigations conducted by Qi Yang and Hao Peng, all patients were treated with radiotherapy using the IMRT technique. However, in our study, only 17% of patients received treatment using the 3D-CRT approach. This difference in treatment approach likely affected survival outcomes, as demonstrated in several other studies.^21,22

Factors affecting DFS

DFS by age group

We observed a significant correlation (p < 0.05) between the DFS rate and age group. The DFS rate in patients aged 50 and below was higher compared to those over 50 (Figure S4). Our study produced similar results to G. Fountzilas 2012 study, which looked at 144 patients with stage II–IVB NPC according to the AJCC 2002 classification and used both induction chemotherapy and CRT.²³ This study demonstrated that Log-rank testing in a univariate analysis of OS by age group (<50; ≥50) yielded a p-value of 0.039. Multivariate analysis using the Cox model also revealed differences in OS and progression-free survival rates between the two age groups (<50 and ≥50).²⁴ The majority of research on the prognostic impact of age on patients with NPC indicates that younger patients generally have a higher OS rate.^25,26 Age also affects survival rates related to disease, local control, and distant metastasis, according to other studies.²⁶ The fact that older patients are more likely to have comorbidities and poorer general health, which can contribute to a lower tolerance for aggressive treatments (radiotherapy and/or chemotherapy), may explain this. Additionally, older patients often present to the hospital later in the disease course and exhibit poorer adherence to treatment compared to younger individuals.

Tumor, node, and disease stage-related DFS

There was no statistically significant difference in DFS rates when considering the T stage (p > 0.05). The 2-year DFS rates were 66.7% for patients with T1 stage tumors, 85.7% for T2 stage tumors, 88% for T3 stage tumors, and 67.9% for T4 stage tumors (Table S3).

Regarding the N stage, there was a statistically significant disparity in DFS (p < 0.05). Patients who had no lymph node involvement (N0) or involvement of only one lymph node (N1) had a DFS rate of 100% at the two-year mark. The individuals with N2 and N3 nodes had corresponding rates of 77.3% and 61.5%, respectively (Table S3). Large-scale studies utilizing multivariate analysis have revealed that the N stage is an independent prognostic determinant for OS, locoregional recurrence-free survival, DFS, and distant metastasis-free survival.^27,28 Sun et al.⁵ demonstrated that N3 nodal stage is an independent prognostic factor with the highest risk of adverse events in DFS (HR = 3.595, 95% CI 1.306–9.896, p = 0.013). Therefore, our study found a statistically significant reduced DFS rate at N3 stage compared to N1 and N2 stages in univariate analysis, which is consistent with the findings of other prior studies.

Out of the total number of patients, four individuals were diagnosed with stage III disease progression within a span of 24 months, whereas 13 individuals had stage IVA advancement. As a result, individuals with stage III had a DFS rate of 88.9% over a period of two years, while those with stage IVA had a rate of 67.5%. Lymph node involvement and disease stage have a substantial impact on DFS, as demonstrated by the Log-rank test in univariate analysis. The p-values for lymph node involvement and disease stage are 0.046 and 0.031, respectively, both indicating statistical significance at the p < 0.05 level (Table S3).

Radiotherapy delay-related DFS

In the context of chemoradiotherapy, patients who experience a delay in completing their treatment for more than 7 days have a negative impact on their DFS compared to patients who have a delay of 7 days or less (Figure S4).

Our findings are consistent with those of other studies.^29,30 For instance, Yao et al.'s³¹ study indicated that an interruption of more than 7 days is detrimental to prognosis (5-year OS: 82.4% vs. 86.5%, p = 0.001). The duration of interruption was also confirmed as an independent prognostic factor through multivariate analysis (HR = 1.49, 95% CI = 1.14–1.95, p = 0.003).³¹ However, there are differences in the time points used to assess treatment delay, potentially due to varying radiotherapy schedules across studies (70 Gy/35 fractions, 70 Gy/33 fractions, 68 Gy/30 fractions) and different methods of calculating total radiotherapy time (Yao et al. assumed treatment initiation on a Monday, whereas other studies used actual dates). As a result, these time points are approximate.

Initiating treatment at the appropriate time is essential, as prolonged radiation and interruptions can negatively impact on patient outcomes. According to a study, there was a 1% decline in the local control rate for each week that passed between the diagnosis and the start of treatment in patients with head and neck cancer. Furthermore, after an average waiting period of 28 days, 62% of patients experienced a 46% increase in tumor volume, and 20% developed lymph node metastases.³² This phenomenon can be explained by tumor tissue undergoing faster regeneration than normal tissue. As a result, the rapid cellular regeneration during the waiting period leads to a reduced biological radiation dose in comparison to the planned treatment volume. The mean duration between the initiation of radiotherapy and the commencement of the last chemotherapy cycle was 45 ± 14 days, ranging from a minimum of 28 days to a maximum of 110 days.

The influence of discontinuing radiation on patient prognosis can be elucidated through various processes, including:

– Radiotherapy interruptions lasting for approximately one week can reduce the biological efficacy of radiation on tumor masses, resulting in potentially reversible cellular harm. During the initiation of radiotherapy, a significant number of tumor cells are located at a considerable distance from capillaries, therefore existing in a hypoxic state. These cells are currently in a quiescent or slow-proliferating condition, exhibiting a markedly reduced rate of proliferation compared to their original pace. Moreover, tumor cells commonly have heightened mortality during the initial stages of treatment, particularly in larger tumors. As radiotherapy progresses, the size of tumors decreases and there is an improvement in vascular distribution. As a result, cells that have not been eliminated by radiation treatment receive enhanced oxygen supply and begin to proliferate at a faster pace.

– Toxicity: The study revealed that most toxicities were categorized as grade I or II, with mucositis and leukopenia being the most prevalent. No significant problems or deaths occurred because of side effects during the treatment course. Our research found that there were fewer cases of severe toxicity (grades III and IV) compared to the study conducted by Zhang et al.⁶ This difference may be attributed to our proactive approach in preventing adverse effects such as nausea, vomiting, diarrhea, mucositis, and allergic reactions. As a result, we have implemented a proactive approach to preventing and managing side effects during and after chemotherapy. This includes administering antiemetic and antishock medications, ensuring proper hydration on chemotherapy days, and closely monitoring patients for 7–10 days to promptly address any potential complications.

The key takeaway from this study highlights the effectiveness and tolerability of induction chemotherapy with gemcitabine and cisplatin, followed by CRT for stage III–IVA NPC. Our findings indicate high rates of tumor response (93.8% achieving CR) while maintaining a manageable toxicity profile. This suggests that, with proactive toxicity management, the treatment regimen offers a balanced approach between efficacy and safety.

Our study contributes to the current literature by providing real-world data on the tolerability of platinum-based chemoradiotherapy regimens, especially for patients in advanced stages who may struggle with high toxicity levels. By documenting specific toxicity rates and detailing the supportive care strategies used, our findings can guide clinicians in managing similar patient populations more effectively. Notably, the high incidence of grade I and II toxicities in this study, accompanied by the relatively low incidence of severe toxicities, highlights the importance of structured supportive care, particularly for mitigating toxicities like neutropenia, mucositis, and nausea.

Limitations

Our study has limitations due to its retrospective nature, including potential confounding factors and a small patient cohort, which could affect the outcomes and limit the statistical power to identify significant associations. This low sample size may result in underpowered findings that should be interpreted with caution. Additionally, while plasma/serum EBV DNA has emerged as an important prognostic biomarker, our study lacks this data due to incomplete records, potentially limiting our ability to comprehensively evaluate all relevant prognostic factors.^33,34 Furthermore, variations in the treatment regimens among patients, such as the use of 3D-CRT radiation and interruptions due to toxicity, the COVID-19 pandemic, or equipment malfunctions, may have introduced biases or variability in the treatment outcomes. These factors should be considered when interpreting the findings, and future studies with larger sample sizes and complete data sets are recommended to validate these observations.

Conclusions

The use of gemcitabine and cisplatin induction chemotherapy may show a positive response in patients with stage III to IVA NPC. This treatment appears to lead to a favorable 2-year DFS rate and may be well-tolerated in terms of side effects. However, as this is an observational study, further research is necessary to confirm these potential benefits and to assess long-term outcomes.

Supplemental Material

sj-docx-1-sci-10.1177_00368504241312582 - Supplemental material for Gemcitabine and cisplatin induction chemotherapy followed by concurrent chemoradiotherapy for stage III–IVA nasopharyngeal carcinoma: A real-world study

Supplemental material, sj-docx-1-sci-10.1177_00368504241312582 for Gemcitabine and cisplatin induction chemotherapy followed by concurrent chemoradiotherapy for stage III–IVA nasopharyngeal carcinoma: A real-world study by Dang Nguyen Van, Son Nguyen Viet and Gia Hoang Phu in Science Progress

Supplemental Material

sj-docx-2-sci-10.1177_00368504241312582 - Supplemental material for Gemcitabine and cisplatin induction chemotherapy followed by concurrent chemoradiotherapy for stage III–IVA nasopharyngeal carcinoma: A real-world study

Supplemental material, sj-docx-2-sci-10.1177_00368504241312582 for Gemcitabine and cisplatin induction chemotherapy followed by concurrent chemoradiotherapy for stage III–IVA nasopharyngeal carcinoma: A real-world study by Dang Nguyen Van, Son Nguyen Viet and Gia Hoang Phu in Science Progress

Supplemental Material

sj-docx-3-sci-10.1177_00368504241312582 - Supplemental material for Gemcitabine and cisplatin induction chemotherapy followed by concurrent chemoradiotherapy for stage III–IVA nasopharyngeal carcinoma: A real-world study

Supplemental material, sj-docx-3-sci-10.1177_00368504241312582 for Gemcitabine and cisplatin induction chemotherapy followed by concurrent chemoradiotherapy for stage III–IVA nasopharyngeal carcinoma: A real-world study by Dang Nguyen Van, Son Nguyen Viet and Gia Hoang Phu in Science Progress

Footnotes

Author contributions

Dang Nguyen Van was the principal investigator, leading the study design, data analysis, and drafting of the manuscript. Son Nguyen Viet, as the senior author and corresponding author, provided key oversight, guided the research methodology, and critically revised the manuscript. Gia Hoang Phu contributed to data collection and assisted with patient management and preliminary data interpretation. All authors read and approved the final version of the manuscript.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Data availability

The data sets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

ORCID iDs

Dang Nguyen Van

Son Nguyen Viet

Supplemental material

Supplemental material for this article is available online.

References

Global Cancer Statistics 2022.pdf. Accessed July 23, 2024. [Online]. Available: https://doi.org/10.3322/caac.21262.

Global Cancer Statistics in Vietnam 2022.pdf. Accessed July 23, 2024. [Online]. Available: http://doi:10.1002/ijc.33588

Alsafadi

Alqarni

Attar

, et al. Nasopharyngeal cancer: prevalence, outcome, and impact on health-related quality of life at Princess Norah Oncology Center, Jeddah, Saudi Arabia. Cureus 2020; 12: e8199.

Al-Sarraf

LeBlanc

Giri

, et al. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized intergroup study 0099. J Clin Oncol Off J Am Soc Clin Oncol 1998; 16: 1310–1317.

Sun

Chen

, et al. Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial. Lancet Oncol 2016; 17: 1509–1520.

Zhang

Chen

, et al. Gemcitabine and cisplatin induction chemotherapy in nasopharyngeal carcinoma. N Engl J Med 2019; 381: 1124–1135.

Zhang

Chen

, et al. Final overall survival analysis of gemcitabine and cisplatin induction chemotherapy in nasopharyngeal carcinoma: a multicenter, randomized phase III trial. J Clin Oncol Off J Am Soc Clin Oncol 2022; 40: 2420–2425.

Hong

Hsiao

Ting

, et al. Final results of a randomized phase III trial of induction chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in patients with stage IVA and IVB nasopharyngeal carcinoma-Taiwan Cooperative Oncology Group (TCOG) 1303 Study. Ann Oncol Off J Eur Soc Med Oncol 2018; 29: 1972–1979.

Chen

Zhang

, et al. Concurrent chemoradiotherapy with/without induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma: long-term results of phase 3 randomized controlled trial. Int J Cancer 2019; 145: 295–305.

10.

Wang

, et al. Induction chemotherapy regimen of docetaxel plus cisplatin versus docetaxel, cisplatin plus fluorouracil followed by concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: preliminary results of an open-label, noninferiority, multicentre, randomised, controlled phase 3 trial. eClinicalMedicine 2022; 53: 101625.

11.

Bongiovanni

Vagheggini

Fausti

, et al. Induction chemotherapy plus concomitant chemoradiotherapy in nasopharyngeal carcinoma: an updated network meta-analysis. Crit Rev Oncol Hematol 2021; 160: 103244.

12.

von Elm

Altman

Egger

, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Ann Intern Med 2007; 147: 573–577.

13.

Zhao

Zhou

Shi

, et al. Clinical outcome for nasopharyngeal carcinoma with predominantly WHO II histology treated with intensity-modulated radiation therapy in non-endemic region of China. Oral Oncol 2012; 48: 864–869.

14.

Zhou

Shi

, et al. Treatment outcomes and late toxicities of 869 patients with nasopharyngeal carcinoma treated with definitive intensity modulated radiation therapy: new insight into the value of total dose of cisplatin and radiation boost. Oncotarget 2015; 6: 38381–38397.

15.

Lee

Foo

Law

, et al. Recurrent nasopharyngeal carcinoma: the puzzles of long latency. Int J Radiat Oncol Biol Phys 1999; 44: 149–156.

16.

Kuderer

Choueiri

Shah

, et al. Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study. Lancet Lond Engl 2020; 395: 1907.

17.

Rucinska

Nawrocki

. COVID-19 pandemic: impact on cancer patients. Int J Environ Res Public Health 2022; 19: 12470.

18.

Huang

, et al. Clinical features of 337 patients with recurrent nasopharyngeal carcinoma. Chin J Cancer 2010; 29: 82–86.

19.

Yang

Cao

Guo

, et al. Induction chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: long-term results of a phase III multicentre randomised controlled trial. Eur J Cancer Oxf Engl 1990 2019; 119: 87–96.

20.

Peng

Chen

Zhang

, et al. Induction chemotherapy improved long-term outcomes of patients with locoregionally advanced nasopharyngeal carcinoma: a propensity matched analysis of 5-year survival outcomes in the era of intensity-modulated radiotherapy. J Cancer 2017; 8: 371–377.

21.

Moon

Cho

Lee

, et al. IMRT vs. 2D-radiotherapy or 3D-conformal radiotherapy of nasopharyngeal carcinoma : survival outcome in a Korean multi-institutional retrospective study (KROG 11-06). Strahlenther Onkol Organ Dtsch Rontgengesellschaft Al 2016; 192: 377–385.

22.

Kristensen

Kjaer-Kristoffersen

Sapru

, et al. Nasopharyngeal carcinoma. Treatment planning with IMRT and 3D conformal radiotherapy. Acta Oncol Stockh Swed 2007; 46: 214–220.

23.

Amin

Greene

Edge

, et al. The Eighth Edition AJCC Cancer Staging Manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin 2017; 67: 93–99.

24.

Fountzilas

Ciuleanu

Bobos

, et al. Induction chemotherapy followed by concomitant radiotherapy and weekly cisplatin versus the same concomitant chemoradiotherapy in patients with nasopharyngeal carcinoma: a randomized phase II study conducted by the Hellenic Cooperative Oncology Group (HeCOG) with biomarker evaluation. Ann Oncol Off J Eur Soc Med Oncol 2012; 23: 427–435.

25.

Gao

Huang

, et al. Nasopharyngeal carcinoma treated by radical radiotherapy alone: ten-year experience of a single institution. Int J Radiat Oncol Biol Phys 2006; 65: 161–168.

26.

Liu

Luo

Liu

, et al. Treatment results and prognostic analysis of 1093 primary nasopharyngeal carcinoma: the experience of a single institution of Guangzhou in the beginning of the 21st century. Chin-Ger J Clin Oncol 2008; 7: 187–195.

27.

Mao

Tang

Chen

, et al. Prognostic factors and failure patterns in non-metastatic nasopharyngeal carcinoma after intensity-modulated radiotherapy. Chin J Cancer 2016; 35: 03.

28.

Ngan

RKC

AWY

, et al. Treatment outcomes of nasopharyngeal carcinoma in modern era after intensity modulated radiotherapy (IMRT) in Hong Kong: a report of 3328 patients (HKNPCSG 1301 study). Oral Oncol 2018; 77: 16–21.

29.

Zhu

. Effect of interrupted time during intensity modulated radiation therapy on survival outcomes in patients with nasopharyngeal cancer. Oncotarget 2017; 8: 37817–37825.

30.

Wang

Feng

Fan

, et al. Clinical outcomes and prognostic factors of 695 nasopharyngeal carcinoma patients treated with intensity-modulated radiotherapy. BioMed Res Int 2014; 2014: 814948.

31.

Yao

Zhang

Gao

, et al. Survival impact of radiotherapy interruption in nasopharyngeal carcinoma in the intensity-modulated radiotherapy era: a big-data intelligence platform-based analysis. Radiother Oncol J Eur Soc Ther Radiol Oncol 2019; 132: 178–187.

32.

Jensen

Nellemann

Overgaard

. Tumor progression in waiting time for radiotherapy in head and neck cancer. Radiother Oncol J Eur Soc Ther Radiol Oncol 2007; 84: 5–10.

33.

Guo

Tang

Mao

, et al. Proposed modifications and incorporation of plasma Epstein–Barr virus DNA improve the TNM staging system for Epstein–Barr virus-related nasopharyngeal carcinoma. Cancer 2019; 125: 79–89.

34.

, et al. Assessment of survival model performance following inclusion of Epstein–Barr virus DNA status in conventional TNM staging groups in Epstein–Barr virus-related nasopharyngeal carcinoma. JAMA Netw Open 2021; 4: e2124721.

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