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 Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 11  |  Issue : 6  |  Page : 191-195

Meta-analysis of concurrent chemoradiotherapy in the treatment of locoregionally advanced nasopharyngeal carcinoma


1 Department of Hand Surgery, China-Japan Union Hospital of Jilin University, Changchun 130031, China
2 Department of Thyroid Surgery, Second Hospital of Jilin University, Changchun 130041, Jilin, China

Date of Web Publication26-Oct-2015

Correspondence Address:
Hong Zhang
Second Hospital of Jilin University, Changchun 130041
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.168183

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 > Abstract 

Background: With radiotherapy (RT) alone, the five-year overall survival (OS) rate for advanced nasopharyngeal carcinoma (NPC) can only reach 40%, the ratio of distant metastasis (DM) is 36–40%. This meta-analysis was performed to compare the clinical efficacy of concurrent chemoradiotherapy (CCRT) with RT alone in the treatment of locoregionally advanced NPC.
Methods: The related literature were retrieved and reviewed by two independent investigators from the followed electronic databases: Review manager 5.3 software (Cochrane Collaboration, London, United Kingdom) was applied for statistical analysis.
Results: A total of 16 trials with 2576 patients were recruited according to the criterion. The odds ratios of 3 and 5 years OS was 0.53 (95% confidence interval [95% CI]: 0.44–0.64) and 0.58 (95% CI: 0.48–0.71), which confirmed the significant improvement of CCRT compared with RT alone (P < 0.001). CCRT also reduced the risk of locoregional control failure and DM in locoregionally advanced NPC patients.
Conclusions: The results suggested that CCRT was more beneficial when compared with RT alone in locoregionally advanced NPC patients. Further study is needed to perform to confirm this effect.

Keywords: Concurrent chemoradiotherapy, meta-analysis, nasopharyngeal carcinoma, radiotherapy


How to cite this article:
Wang Y, Ding W, Chen C, Niu Z, Pan M, Zhang H. Meta-analysis of concurrent chemoradiotherapy in the treatment of locoregionally advanced nasopharyngeal carcinoma. J Can Res Ther 2015;11, Suppl S2:191-5

How to cite this URL:
Wang Y, Ding W, Chen C, Niu Z, Pan M, Zhang H. Meta-analysis of concurrent chemoradiotherapy in the treatment of locoregionally advanced nasopharyngeal carcinoma. J Can Res Ther [serial online] 2015 [cited 2019 Dec 15];11:191-5. Available from: http://www.cancerjournal.net/text.asp?2015/11/6/191/168183


 > Introduction Top


Nasopharyngeal carcinoma (NPC) is a distinct type of head and neck cancer that arises from the epithelial cells of the nasopharynx. It is a leading form of cancer in endemic regions such as Southern China, where the incidence is 25 cases per 10,000.[1] Radiotherapy (RT) is a mainstay of NPC treatment because of the tumor's sensitivity to this approach and the anatomical constraints for surgery. With RT alone, the five-year overall survival (OS) rate for early-stage NPC can reach over 90%.[2] However, the five-year OS rate for advanced NPC can only reach 40%, the ratio of distant metastasis (DM) is 36–40%, and up to 70% of patients present with advanced (Stages III–IV) disease at the time of diagnosis.[3] The study was planned to make the meta-analysis for comparing the clinical trial data of concurrent chemoradiotherapy (CCRT) with RT alone and explored whether CCRT have a positive effect on the prognosis of NPC.


 > Methods Top


Data sources and search strategy

An electronic search on the PubMed database, Cochrane library database, Chinese Academic Journal Articles, and CNKI were performed. The published language includes English and Chinese. The topic retrieval words include nasopharyngeal cancer/NPC, CCRT, RT, and randomized controlled trials.

Data selection and exclusion criteria

The data selection was performed by two reviewers independently. Studies were included if they were randomized, controlled trials. The study population must include the adult patients with Stage III or IV, nonmetastatic NPC according to the tumor node metastasis system. The follow-up years must more than 3–5 years. The study was excluded if they were a nonprospective randomized study, or they were the study which exist neoadjuvant chemotherapy in the CCRT. The eligibility of each citation was independently assessed by two unblended reviewers, and disagreements were resolved by the discussion or a third party.

Data extraction criteria

The data extraction was performed by two reviewers independently. The following study characteristics were recorded for each trial: Grouping method, blinding set, withdrawal and exit, baseline study, and control of confounding factors.

Quality assessment

According to the Jadad scale, a five-point scale system, was used to evaluate the methodological quality of trials, the score of 16 trials selected in this study was from 3 to 5.

Statistical analysis

Statistical analyses were performed by RevMan 5.3 offered by Cochrane Collaboration network and RevMan can make statistical analysis of large collection of analysis results from individual studies for the purpose of integrating the findings. The efficacy analysis and statistics of this paper were measured by odds ratio. The effect amount of is described with 95% confidence interval (95% CI). The heterogeneity analysis between the groups was carried out via the Chi-square test, fixed effects model was applied when there is no heterogeneity (P > 0.10). Otherwise, it would be analyzed through the random effects model. At the same time, we should analyze why there is heterogeneity. I2 was quantitative analysis values indicated that the difference among the effect size of different studies. When I2 was more than 50%, there would being exist the substantive heterogeneity possibly among different studies.


 > Results Top


Search results

For the entire patient population, a total of 16 studies involving 2576 patients [1],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18] were reported through the literature search. Seven Chinese literature and English literature were selected.

The patients were divided into a high-risk group and low-risk group by Lin et al. in terms of the degree of risk. Because both the groups met the inclusion criteria, therefore, it is as two independent studies were analyzed. The studies of Kwong et al. were included CCRT, adjuvant chemotherapy and CCRT plus adjuvant chemotherapy, and three different kinds of treatment mode. In this study, we only extract CCRT and CCRT plus adjuvant chemotherapy, this two groups of patient data, denoted as Kwong et al.[5] RT group was used as control group. The reference of 10th was repeated partly as compared to the reference of 8th. We only extract the data not duplicated.

Overall survival results

Three years OS data were available in 16 studies, because P > 0.10 (P = 0.17) and I2 < 50% (I2 = 25%), explaining that there is no heterogeneity among these trials. Hence, we apply the fixed effects model. The merge odds ratio (OR) was 0.53 (95% CI: 0.44–0.64), P > 0.00001, indicating that 3 years the death risk of CCRT group was lower 47% than RT group. The difference was statistically significant. The forgetting results illustrate that CCRT can increase 3 years the OS obviously. The results were shown in [Figure 1].
Figure 1: Three years overall survival of concurrent chemoradiotherapy versus radiotherapy

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Nine studies were identified about 5 years OS, because P > 0.10 (P = 0.21) and I2 < 50% (I2 = 26%), implying that there is no heterogeneity among these trials. Hence, we apply the fixed effects model. The merge OR was 0.58 (95% CI: 0.48–0.71), P > 0.00001, suggesting that 5 years the death risk of CCRT group was lower 42% than RT group. The difference was statistically significant, illustrate that CCRT can increase 5 years the OS obviously. The results were shown in [Figure 2].
Figure 2: Five years overall survival of concurrent chemoradiotherapy versus radiotherapy

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Locoregional control failure rate

Eleven trials were contained for 3 years locoregional control failure (LRCF) rate. Because P > 0.10 (P = 0.25) and I2 < 50% (I2 = 21%), stating that there is no heterogeneity among these trials. Hence, we apply the fixed effects model. The OR was 0.50 (95% CI: 0.37–0.66), implicating that the risk of 3 years LRCF rate of CCRT group was lower 51% than RT group. The difference was statistically significant. That is to say, CCRT can decrease 3 years LRCF rate obviously. The results were shown in [Figure 3].
Figure 3: Three years locoregional control failure rate of concurrent chemoradiotherapy versus radiotherapy

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Seven trials were reported about 5 years LRCF rate. Because P > 0.10 (P = 0.13) and I2 < 50% (I2 = 39%), suggesting that there is no heterogeneity among these trials. Hence, we apply the fixed effects model. The merge OR was 0.43 (95% CI: 0.31–0.60), P < 0.00001, suggesting that the risk of 5 years LRCF of CCRT group was lower 57% than RT group. The difference was statistically significant. The forgetting results illustrate that CCRT can decrease 5 years LRCF rate obviously. The results were shown in [Figure 4].
Figure 4: Five years locoregional control failure rate of concurrent chemoradiotherapy versus radiotherapy

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Distant metastasis

The total eight trials were found of 3 years DM. Because P < 0.10 (P = 0.06), pointing that there is heterogeneity among these trials. We are supposed to apply the random effects model. However, I2 < 50% (I2 = 48%), implicated that there is no substantive heterogeneity. However, hyperfractionated, accelerated RT was applied in Lee et al. 2006; others adopted the conventional RT, so we continued the analyzing after deleting Lee 2006. This time showed that P was more than 0.10 (P = 0.13) and I2 < 50% (I2 = 39%), indicating that there is no substantive heterogeneity. The merge OR was 0.59 (95% CI: 0.45–0.76), P < 0.001, consistent with original analysis, giving that high stability of the results. The difference was statistically significant; displaying that the risk of 3 years DM of CCRT group was lower 41% compared to RT group. The forgetting results suggest that CCRT can decrease the risk of 3 years DM obviously. The results were shown in [Figure 5] and [Figure 6].
Figure 5: Three years distant metastasis of concurrent chemoradiotherapy versus radiotherapy

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Figure 6: Three years distant metastasis of concurrent chemoradiotherapy versus radiotherapy (excluded of Lee 2006)

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There were six studies involving the risk of 5 years DM. The heterogeneity analysis showed that P > 0.10 (P = 0.31) and I2 < 50% (I2 = 16%), implying that there is no substantive heterogeneity, so we apply fixed effects model. The merge OR was 0.48 (95% CI: 0.34–0.68), P < 0.001. There was statistically significant. Because the risk of 5 years DM of CCRT group is lower 52% than RT group, point that CCRT can decrease the risk of 5 years DM obviously. The results were shown in [Figure 7].
Figure 7: Five years distant metastasis of concurrent chemoradiotherapy versus radiotherapy

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 > Discussion and Conclusions Top


Currently, RT is the primary treatment modality for nondisseminated NPC because of the anatomical location and radiosensitivity. However, the efficacy for locoregionally advanced NPC is not desirable due to the local recurrence and DM. CCRT has proven to be the key component in the treatment of locoregionally advanced NPC, and neither induction nor adjuvant chemotherapy has an additional impact on survival.[19],[20] The advent of CCRT local control has been substantially improved, and DM has been decreased.[21] Chemotherapy can decrease the tumor burden; control the DM, synergies with RT. This meta-analysis compared the efficacy in the treatment of locoregionally advanced NPC.

CCRT can increased 3 and 5 years OS. Three years the death risk of CCRT group was lower 47% than RT group and 5 years the death risk of CCRT group was lower 42% than RT group. Because the drug applied in chemotherapy can make the tumor of nasopharyngeal more sensitive to RT. In additional CCRT can decreased 3 and 5 years local recurrence rate and 3 and 5 years DM rate, the risk of 3 years LRCF rate of CCRT group was lower 51% than RT group and the risk of 5 years LRCF of CCRT group was lower 57% than RT group; the risk of 3 years DM of CCRT group was lower 41% compared to RT group and the risk of 5 years DM of CCRT group is lower 52% than RT group. Indicated that CCRT had a more sharp lethality to the tumor of nasopharyngeal and can remove the tumor more cleanly compared to RT. However, this study only analyzed the data published, cannot get the patient information. Hence, some problems cannot be expressed precisely. There would be exist bias. Moreover, CCRT can increase the adverse reactions, which would have an effect on treatment by reducing the tolerance of patients. It would bring a difficulty to further treatment. Based on that, it was especially important to develop the drugs of low toxicity and having stronger of enhancing sensitivity to minimizing the radiation dose. What is more, we can improve the quality of life of patients by improving the mode of administration. More studies are also warranted to define the value of induction or adjuvant treatment in the specific patient subgroups, or the effect of different drug combinations. Other potential avenues of research include exploring the use of chemotherapy in the context of relatively new treatment options, such as intensity-modulated radiation therapy and immunotherapy.

Taken together, how to choose the best drug and determine the radiation dose, how to reduce the toxicity and determine the cycle of treatment need further be explored, only by doing that can we design the novel therapeutic strategies.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 > References Top

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]



 

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