The efficacy of chemotherapy in survival of stage II nasopharyngeal carcinoma

doi:10.1016/j.oraloncology.2019.104520

Oral Oncology

Volume 101, February 2020, 104520

https://doi.org/10.1016/j.oraloncology.2019.104520 Get rights and content

Highlights

•
Chemoradiotherapy does not improve 5-year overall survival compared with radiotherapy of stage II nasopharyngeal carcinoma.
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Chemoradiotherapy shows a comparable 5-year cancer-specific survival compared to radiotherapy of stage II nasopharyngeal carcinoma.

Abstract

Purpose

Chemotherapy use remains controversial for stage II nasopharyngeal carcinoma (NPC). This retrospective study was conducted to identify whether chemoradiotherapy was associated with better survival compared to radiotherapy.

Materials and methods

The Surveillance, Epidemiology, and End Results (SEER) database was queried for stage II NPC patients between 2004 and 2015. Patients were divided into radiotherapy and chemoradiotherapy groups. Overall survival (OS) and cancer-specific survival (CSS) were examined using the Kaplan-Meier method, Cox proportional hazards models, and propensity score matching analyses.

Results

This study examined 908 patients, including 102 receiving radiotherapy and 806 receiving chemoradiotherapy. Chemoradiotherapy was associated with 5-year OS (78.01% vs. 75.12%; p = 0.22) and CSS (78.92% vs. 78.26%; p = 0.40) rates comparable to those of radiotherapy. Propensity score matching analyses demonstrated similar OS (HR: 0.63, 95% CI: 0.36–-1.10; p = 0.10) and CSS (HR: 0.77, 95% CI: 0.41–1.48; p = 0.44) rates with radiotherapy. Age >60 years and non-Asian patients were associated with worse survival.

Conclusion

This study revealed that chemoradiotherapy showed similar survivals to stage II NPC patients compared with radiotherapy. Due to the limitations of SEER database, further studies should be performed to verify the results.

Introduction

Nasopharyngeal carcinoma (NPC) is a highly epidemiologic and radiosensitive cancer [1]. Radiotherapy alone is recommended for stage I NPC [2], while the addition of chemotherapy to radiotherapy improves the survival of patients with locoregionally advanced NPC [3], [4], [5]. However, chemotherapy use remains controversial for stage II NPC. A phase III randomized controlled trial revealed improved 5-year overall survival (OS) rates in Chinese patients with stage II NPC who received concurrent chemoradiotherapy compared to radiotherapy alone (94.5% vs. 85.8%; p = 0.007) [6]. In contrast, it was reported that radiotherapy alone could provide satisfactory treatment outcomes [7]. Chemotherapy use did not improve OS [8], [9], [10], [11], [12]. Moreover, chemoradiotherapy causes more acute and later toxicity reactions [6], [8], [13], thus leading to poorer quality of life [14].

The incidence of stage II NPC has greatly increased with improvements in diagnosis. Moreover, a majority of stage II NPC patients are still receiving chemotherapy [15]. Thus, it is urgent to identify the role of chemotherapy in stage II NPC. The object of this retrospective cohort study was to identify whether chemoradiotherapy is associated with better survival outcomes compared to radiotherapy alone in stage II NPC.

Section snippets

Patients

The Surveillance, Epidemiology, and End Results (SEER) database was queried for NPC patients between 2004 and 2015. Inclusion criteria were as follows: (1) pathologic confirmed NPC; (2) stage II (T1N1, T2N0, and T2N1) patients according to the American Joint Committee on Cancer (AJCC) staging system; and (3) patients who received radiotherapy. Exclusion criteria were as follows: (1) patients who did not receive any treatment; (2) patients with an unknown cause of death; and (3) patients with a

Patient characteristics

This study examined 908 stage II NPC patients, including 102 (11.23%) receiving radiotherapy and 806 (88.77%) receiving chemoradiotherapy. The median follow-up times were 57.5 [interquartile range (IQR): 28–98] months, 56.5 (IQR: 29–86) months, and 58.0 (IQR: 28–99) months for the whole stage II group, the radiotherapy group, and the chemoradiotherapy group, respectively. Chemotherapy use was significantly associated with N1 stage. In the radiotherapy group, 55 (53.92%) patients were in N1

Discussion

This study revealed that 88.77% of patients with stage II NPC were treated with chemoradiotherapy. However, chemotherapy did not improve the survival of patients with stage II NPC. Among this subset of patients, Asian patients showed better survival compared to White patients. Patients aged >60 years were associated with poor treatment outcomes.

Whether induction chemotherapy and adjuvant chemotherapy are associated with treatment outcomes for stage II NPC remains unclear due to the limited

Declaration of Competing Interest

The authors declared that there is no conflict of interest.

Acknowledgements

This study was supported by a grant from the Department of Education of Guangxi Zhuang Autonomous Region (No. KY2016LX029), a grant from Guangxi Medical University (No. GXMUYSF201519) and a grant from the Research and Development Project of Guangxi (No. 1598012-22).

Funding source

None declared.

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Cited by (19)

Significance of chemotherapy for older patients with nasopharyngeal carcinoma in the intensity-modulated radiotherapy era: A propensity score matching analysis
2023, Journal of Geriatric Oncology
This study aimed to evaluate the survival and prognosis of older patients with nasopharyngeal carcinoma (NPC) who received intensity-modulated radiotherapy (IMRT) alone versus IMRT plus chemotherapy using propensity score matching (PSM).
We enrolled 841 older patients with NPC aged 60 years and above without metastasis receiving IMRT alone or chemoradiotherapy from 2012 to 2019. The comorbidity was assessed by adult comorbidity evaluation (ACE-27). PSM (1:3 ratio) was conducted between the two treatment groups based on four clinical factors including age, T-stage, N-stage, and ACE-27. Differences in overall survival (OS) and cancer-specific survival (CSS) were analyzed by the Kaplan-Meier method and Cox proportional hazard model.
A total of 841 patients with NPC were included in the study, there were 94 patients in the IMRT alone group and 747 patients in the chemoradiotherapy (CRT) group. After a 1:3 ratio PSM, 89 patients underwent IMRT alone and 223 patients underwent CRT. The baseline analysis showed an insignificant difference after PSM (P > 0.05). In multivariate analysis, we found that ACE-27 (≥2) was associated with worse five-year OS and CSS (HR = 1.994, 95%CI: 1.276–3.116, P = 0.002; HR = 1.849, 95%CI: 1164–2.935, P = 0.009, respectively). Chemotherapy was an independent prognosticator of better five-year OS and CSS (HR = 0.333, 95%CI: 0.213–0.552, P < 0.001; HR = 0.327, 95%CI: 0.204–0.524, P < 0.001, respectively). In terms of subgroup analysis, chemotherapy was a statistically beneficial predictor for stage III-IV patients (P < 0.05), but no significant difference in stage II patients (P > 0.05). About the adverse events, the incidence of hepatotoxicity (P = 0.002), neutropenia (P < 0.001), anemia (P < 0.001), and thrombocytopenia (P < 0.001) were significantly higher in the CRT group.
Combined modality therapy was associated with improved five-year OS and CSS in older adults with stage III-IV NPC, but was not associated with improved survival over IMRT alone in patients with stage II disease. Risk factors including T3–4 disease, positive lymph nodes, ACE-27 score ≥ 2, and IMRT alone were were associated with worse OS and CSS. There was a significantly higher incidence of hepatotoxicity and blood toxicity in the CRT group.
MRI-based deep learning model predicts distant metastasis and chemotherapy benefit in stage II nasopharyngeal carcinoma
2023, iScience
Chemotherapy remains controversial for stage II nasopharyngeal carcinoma because of its considerable prognostic heterogeneity. We aimed to develop an MRI-based deep learning model for predicting distant metastasis and assessing chemotherapy efficacy in stage II nasopharyngeal carcinoma. This multicenter retrospective study enrolled 1072 patients from three Chinese centers for training (Center 1, n = 575) and external validation (Centers 2 and 3, n = 497). The deep learning model significantly predicted the risk of distant metastases for stage II nasopharyngeal carcinoma and was validated in the external validation cohort. In addition, the deep learning model outperformed the clinical and radiomics models in terms of predictive performance. Furthermore, the deep learning model facilitates the identification of high-risk patients who could benefit from chemotherapy, providing useful additional information for individualized treatment decisions.
The role of radiologic extranodal extension in predicting prognosis and chemotherapy benefit for T1-2 N1 nasopharyngeal carcinoma: A multicenter retrospective study
2023, Radiotherapy and Oncology
This multicenter retrospective study aimed to investigated the prognostic value of unequivocal radiologic extranodal extension (rENE) and the efficacy of chemotherapy for stage T1-2 N1 nasopharyngeal carcinoma (NPC) in the IMRT era.
We included 1,082 patients treated in 2005–2017 from three centers. rENE was recorded as G1 (coalescent nodal mass comprising ≥ 2 inseparable nodes) or G2 (invading beyond perinodal fat to frankly infiltrate adjacent structures). Multivariable analysis (MVA) evaluated the prognostic value of rENE. The value of chemotherapy was assessed in rENE-positive (rENE + ) and rENE-negative (rENE − ) subset separately.
Centers 1, 2, and 3 had 139/515 (27.0 %), 100/365 (27.4 %), and 43/202 (21.3 %) cN + patients with rENE, respectively. Compared to rENE−, rENE + patients had a worse distant metastasis-free survival (DMFS) and overall survival (OS) (all p < 0.001). MVA confirmed the prognostic of both G1-rENE and G2-rENE for distant metastasis [G1: hazard ratio (HR): 2.933, G2: HR: 6.942, all p < 0.001] and death (G1: HR: 1.587, p = 0.040; G2: HR: 6.162, p < 0.001). There was no significant difference for DMFS and OS between chemo-radiotherapy and radiotherapy alone in rENE + and rENE − groups (all p > 0.1). However, rENE + patients with a cumulative cisplatin/nedaplatin dose (CCND) of > 160 mg/m² had an improved DMFS (p = 0.033) but no OS (p = 0.197).
Unequivocal rENE is prognostic in patients with T1-2 N1 NPC. Addition of chemotherapy to radiotherapy did not affect DMFS and OS in rENE − patients. Chemotherapy with a CCND of > 160 mg/m² improved DMFS in rENE + patients.
Efficacy of chemoradiotherapy in survival of stage Ⅳ nasopharyngeal carcinoma and establishment of a prognostic model
2022, Oral Oncology
Citation Excerpt :
The current recommended regimens for NPC involve stage Ⅱ to Ⅳ, among which chemoradiotherapy is gradually recognized as the standard treatment, while further investigations on its efficacy is needed. On the ground of SEER database analysis, it has been proved that chemoradiotherapy in III NPC reduces the all-cause mortality and cancer-specific mortality, but the treatment effect is not obvious in Ⅱ NPC [7,8]. Despite that the benefit of chemotherapy is not clear, most patients suffering IV NPC are still receiving chemoradiotherapy.
The efficacy of chemoradiotherapy regimen in the treatment of stage Ⅳ nasopharyngeal carcinoma (Ⅳ NPC) is not clear. This retrospective study aimed to reveal the benefit of chemoradiotherapy in Ⅳ-NPC and to develop a survival prognostic model for the disease prediction.
The Surveillance, Epidemiology, and End Results (SEER) database at https://seer.cancer.gov was retrieved for stage Ⅳ NPC patients between 2004 and 2016. The patients were divided into two groups of radiotherapy and chemoradiotherapy according to the treatment method. Overall survival (OS) and cancer-specific survival (CSS) between the groups were compared using Kaplan-Meier analysis, log-rank test, and propensity matching score (PSM). Cox proportional hazards model, nomogram, and receiver operating characteristic (ROC) curve were employed to establish the prognostic model.
A total of 729 patients with Ⅳ NPC were introduced, of whom 44 received radiotherapy and 685 received chemoradiotherapy. Results of statistical tests demonstrated that chemoradiotherapy was associated with improved OS and CSS, especially in the patients with ⅣA NPC (P < 0.05); further multivariate analysis with PSM confirmed that chemoradiotherapy benefited the patients’ OS (HR: 0.24, 95% CI: 0.12–0.50; P < 0.001). Moreover, the efficacy of chemoradiotherapy was found significantly correlated to metastasis. Even though chemoradiotherapy had an obvious survival benefit in patients without metastasis, it only helped to improve the CSS in those with metastases.
This study indicated that chemoradiotherapy could improve the survival of NPC patients at stage ⅣA and non-metastasis. The nomogram we established may provide reference for clinical treatment of NPC.
Benefit of chemotherapy in stage III nasopharyngeal carcinoma: Analysis of the surveillance, epidemiology, and end results database
2021, Oral Oncology
Citation Excerpt :
Our finding agrees with several previous reports in one way or another—the magnitude of chemotherapy benefit in the survival of low-risk NPC warrants investigation. Both retrospective and prospective series and several meta-analyses reported that chemoradiotherapy showed similar survival outcomes in stage II NPC than RT alone [30–34]. In another phase III randomized trial, Chen et al. reported a survival benefit of CCRT, but the benefit was mainly reflected in the T2N1 population.
Chemoradiotherapy is the standard treatment for locoregionally advanced nasopharyngeal carcinoma (NPC). We aimed to reveal factors associated with chemotherapy use and evaluate chemotherapy’s benefit in patients with stage III NPC stratified by lymph node status.
Overall, 1452 patients with stage III NPC who underwent radiotherapy with (n = 1361) or without (n = 91) chemotherapy were identified in the SEER database. We examined predictors for chemotherapy use using logistic regression analysis. We compared all-cause mortality (ACM) and cancer-specific mortality (CSM) using the Kaplan-Meier method. Cox regression and competing risk analyses were used to evaluate the benefit of chemotherapy. The inverse probability of treatment weighting (IPTW) approach was applied to reduce selection bias and adjust for competing risks. Subgroup analyses and interaction effects were explored.
Factors including age, sex, insured status, tumor grade, and N category were associated with chemotherapy use. Chemotherapy was associated with decreased 5-year ACM (31.4% vs. 48.4%, p < 0.001) and CSM (25.5% vs. 35.8%; p = 0.017) in stage III NPC patients. The IPTW-adjusted hazard ratio for 5-year ACM was 0.57 (95% CI: 0.38–0.86, p = 0.008), whereas IPTW-adjusted sub-hazard ratio for 5-year CSM was 0.62 (95% CI: 0.42–0.93, p = 0.003). A significant interaction effect existed between lymph node status and treatment modality. Chemotherapy offered a significant survival benefit in node-positive stage III NPC. However, no chemotherapy benefit for the node-negative disease was observed.
Chemotherapy adds survival benefit in stage III NPC, especially in patients with node-positive disease. The magnitude of chemotherapy benefit in node-negative stage III NPC warrants further investigation.
Use of survival support vector machine combined with random survival forest to predict the survival of nasopharyngeal carcinoma patients
2023, Translational Cancer Research

View all citing articles on Scopus

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The efficacy of chemotherapy in survival of stage II nasopharyngeal carcinoma

Highlights

Abstract

Purpose

Materials and methods

Results

Conclusion

Introduction

Section snippets

Patients

Patient characteristics

Discussion

Declaration of Competing Interest

Acknowledgements

Funding source

Lancet Oncol

Int J Radiat Oncol Biol Phys

Oral Oncol

Oral Oncol

Oral Oncol

Eur J Cancer

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Radiother Oncol

Radiother Oncol

Cancer statistics in China, 2015

CA Cancer J Clin

Patterns of care and outcomes with the addition of chemotherapy to radiation therapy for stage I nasopharyngeal cancer

Acta Oncol

Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099

J Clin Oncol: Off J Am Soc Clin Oncol

Randomized trial of radiotherapy versus concurrent chemoradiotherapy followed by adjuvant chemotherapy in patients with American Joint Committee on Cancer/International Union against cancer stage III and IV nasopharyngeal cancer of the endemic variety

J Clin Oncol: Off J Am Soc Clin Oncol

Concurrent chemoradiotherapy vs radiotherapy alone in stage II nasopharyngeal carcinoma: phase III randomized trial

J Natl Cancer Inst

Long-term outcomes of concurrent chemoradiotherapy versus radiotherapy alone in stage II nasopharyngeal carcinoma treated with IMRT: a retrospective study

Tumour Biol

Long-term survival of nasopharyngeal carcinoma patients with Stage II in intensity-modulated radiation therapy era

Jpn J Clin Oncol

Chemotherapy use and survival in stage II nasopharyngeal carcinoma

Oncotarget

Omission of chemotherapy in early stage nasopharyngeal carcinoma treated with IMRT: a paired cohort study

Medicine

Comparison of the efficacy between concurrent chemoradiotherapy with or without adjuvant chemotherapy and intensity-modulated radiotherapy alone for stage II nasopharyngeal carcinoma

Oncotarget