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  Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 54  |  Issue : 1  |  Page : 223-227
 

The efficacy and safety of preoperative chemotherapy for patients with nonsmall cell lung cancer: A meta-analysis


Department of Thoracic Surgery, Peking University Third Hospital, Beijing 100191, China

Date of Web Publication1-Dec-2017

Correspondence Address:
Dr. T Yan
Department of Thoracic Surgery, Peking University Third Hospital, Beijing 100191
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijc.IJC_60_17

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 » Abstract 

BACKGROUND: The efficacy of surgery alone for patients with nonsmall cell lung cancer (NSCLC) is still unsatisfactory. Preoperative chemotherapy (PCT) is proven effective induction therapies followed by surgery; however, few their superiority remains uncertain. We performed a systemic review and meta-analysis to evaluate the safety and efficacy of the PCT for NSCLC patients. MATERIALS AND METHODS: A literature search was performed in the PubMed, China National Knowledge Infrastructure and Cochrane databases. NSCLC patients treated with PCT plus surgery (PCT-S) or surgery (S) alone between 2006 and 2016 were analyzed. RESULTS: A total of eleven studies, involving a total of 2999 patients, were finally enrolled in this meta-analysis. Meta-analysis shows that PCT-S might have lower recurrence rate than S (odds ratio [OR] = 0.75, 95% confidence interval [CI] [0.60, 0.94], P = 0.01). However, no differences were found between two groups in overall survival rate (OR = 1.26, 95% CI [0.92, 1.72], P = 0.15) and (OR = 1.12, 95% CI [0.93, 1.33], P = 0.23), 3-year disease-free survival rate (OR = 1.22, 95% CI [0.73, 2.04], P = 0.44) and intraoperative and postoperative complication rates (OR = 1.24, 95% CI [0.89,1.74], P = 0.20). CONCLUSIONS: Two treatments have similar safety and efficacy. However, PCT can reduce the rate of local and distant recurrence, which is an independent risk factor for NSCLC prognosis and may improve the prognosis of NSCLC.


Keywords: Meta-analysis, nonsmall cell lung cancer, preoperative chemotherapy, surgery


How to cite this article:
Wang T, Yan T, Ma S, Wang K, Wang J, Song J, He W, Bai J, Jin L. The efficacy and safety of preoperative chemotherapy for patients with nonsmall cell lung cancer: A meta-analysis. Indian J Cancer 2017;54:223-7

How to cite this URL:
Wang T, Yan T, Ma S, Wang K, Wang J, Song J, He W, Bai J, Jin L. The efficacy and safety of preoperative chemotherapy for patients with nonsmall cell lung cancer: A meta-analysis. Indian J Cancer [serial online] 2017 [cited 2020 Mar 31];54:223-7. Available from: http://www.indianjcancer.com/text.asp?2017/54/1/223/219598



 » Introduction Top


Lung cancer is the leading cause of cancer-related death in most countries of the world.[1],[2] According to the pathology and cytology classification, small cell lung cancer and nonsmall cell lung cancer (NSCLC) are two types of lung cancer. NSCLC accounts for more than 80%.[3]

There are different standards for NSCLC treatment. In general, surgical resection is the first choice to treat lung cancer.[4],[5] For patients with Stage I disease, the 5 years survival rates range from between 50% and 70% estimably, but for patients with Stage IIIA disease was 10% and 30% only.[6],[7] To improve survival rates, researchers explore the role of systemic therapy in NSCLC. In the 1990s, several clinical trials found improvements in survival of preoperative chemotherapy (PCT) plus surgery in patients with locally advanced NSCLC.[8],[9] Thus, PCT, with or without resection (preferably lobectomy), is an option for patients.[10]

In a previous study, we identified several randomized trials has been analyzed the efficacy of PCT in NSCLC patients. Although available data suggest survival benefit of PCT, the majority of individual trials have found no statistically significant differences.[11],[12],[13],[14] Hence, the research results about the efficacy and safety of PCT remain a debate. The objective of this study is to perform a meta-analysis of the available data to determine whether PCT is superior to surgery alone in patients with NSCLC.


 » Materials and Methods Top


Literature search

We searched The Cochrane Library, PubMed and China National Knowledge Infrastructure using the following search terms: NSCLC or NSCLC, and PCT or PCT, and surgery to identify the eligible literatures published between May 1, 2006 and May 1, 2016. Besides, we also manually searched the reference lists of original literatures to identify any possible included study.

Inclusion and exclusion criteria

Candidate studies included: (1) Compare the relationship between PCT plus surgery (PCT-S) and surgery alone; (2) all patients are primary lung cancer; (3) provide sufficient original data to estimate the odds ratio (OR) and a corresponding 95% confidence interval (95% CI); (4) be published in English. Studies were excluded: (1) not case-control study; (2) reviews, duplicate of previous publications, case reports, conference abstract; (3) no usable data reported; (4) non-English languages.

Data extraction

Two authors reviewed eligible studies and extracted the following data independently. The first author name; year of publication; research time; the clinical stage of cancer; number of cases and controls; efficacy indicators including survival rate, the disease-free survival rate and recurrence rate; safety indicators including intraoperative and postoperative complication rates (neutropenia, thrombocytopenia, bronchial fistula, pulmonary embolism, nausea and vomiting, respiratory failure, etc.). Disagreements were resolved by discussing with a third investigator.

Statistical analysis

In this meta-analysis, Revman 5.3 was used to performed data analysis and bias risk assessment. We applied the OR with 95% CI as the appropriate summarized statistics. In general, OR with 95% CI could be directly extracted from the published statistical results, or calculated by demographic data if no statistic was reported. In this meta-analysis, fixed or random effects models were used depending on the heterogeneity between studies. Heterogeneity between studies was performed using Q-test and I2 test. When P < 0.05 in Q-test or I2< 50% in I2 test, a fixed-effect model was used to estimate pooled ORs and 95% CIs. Otherwise, a random-effect model was used. In addition, we used funnel plots to judge publication bias.


 » Results Top


Study characteristics

In total, 341 publications were found after database searched systematically. [Figure 1] shows the selection process and specific reasons for exclusion. Finally, 11 full-text papers [11],[12],[15],[16],[17],[18],[19],[20],[21],[22],[23] were included in our meta-analysis, in accordance with the inclusion criteria. A total of 2999 patients in the 11 studies, with 1494 cases in PCT-S group and 1505 cases in S group. [Table 1] summarizes the general situation and baseline characteristics. The differences of clinical stages, patient age, male percentage, and pathological types in included studies were not statistically significant (P > 0.05).
Figure 1: Flow chart

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Table 1: Baseline characteristics of included studies

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Relevant efficacy indicators analysis between preoperative chemotherapy plus surgery group and S group

Nine studies [11],[15],[16],[17],[18],[19],[20],[21],[23] compared 3-year overall survival rates, as shown in [Figure 2]. We used a random effects model for analysis, because of heterogeneity between studies (P = 0.01, I2 = 58%). We found a significant difference between two groups in 3-year overall survival rates (OR = 1.26, 95% CI [0.92, 1.72], P = 0.15) after the meta-analysis. Seven studies [11],[12],[18],[19],[20],[21],[22] compared the 5-year overall survival rates as shown in [Figure 3]. With no heterogeneity between studies (P = 0.33, I2 = 13%), a fixed effects model for analysis was used. The result showed a significant difference between two groups in the 5-year overall survival rates (OR = 1.12, 95% CI [0.93, 1.33], P = 0.23).
Figure 2: Comparison of 3-year overall survival rates between preoperative chemotherapy plus surgery and S

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Figure 3: Comparison of 5-year overall survival rates between preoperative chemotherapy plus surgery and S

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Three studies [11],[19],[22] compared the 3-year disease-free survival rate after treatment [Figure 4]. Due to heterogeneity between studies (P = 0.09, I2 = 58%), we used a random effects model for analysis and did not find a significant difference between two groups in the 3-year disease-free survival rate (OR = 1.22, 95% CI [0.73, 2.04], P = 0.44).
Figure 4: Comparison of disease-free survival rates between preoperative chemotherapy plus surgery and S

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Six studies [11],[12],[16],[17],[18],[23] compared the recurrence rate after treatment between two groups [Figure 5]. There are no heterogeneity between these studies (P = 0.83, I2 = 0%). We used a fixed effects model for analysis. The result show a significant difference in the recurrence rate (OR = 0.75, 95% CI [0.60, 0.94], P = 0.01) between two groups. That means PCT-S might have lower recurrence rate than S. According to the funnel chart [Figure 6], there is no publication bias between PCT-S group and S group in comparison of the rate of recurrence.
Figure 5: Comparison of recurrence rates between preoperative chemotherapy plus surgery group and S group

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Figure 6: Funnel plot for checking publication bias

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Relevant safety indicators analysis between preoperative chemotherapy plus surgery group and S group

Five Researches [11],[15],[16],[17],[21] compared the intraoperative and postoperative complication rates as shown in [Figure 7]. Because of no heterogeneity between studies (P = 0.98, I2 = 0%), we used a fixed effects model for analysis. We did not see a significant difference in the intra- and post-operative complication rates (OR = 1.24, 95% CI [0.89, 1.74], P = 0.20) between two groups.
Figure 7: Comparison of the intra- and post-operative complication rates between preoperative chemotherapy plus surgery group and S group

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Limitations

Finally, several major limitations of this meta-analysis should be acknowledged. First, the number of some prognostic studies was relatively small, which might weaken the reliability of our results. Second, we were unable to further identify the association between detail courses and effect of PCT in this meta-analysis. Third, the current evidences came from many countries. Thus, inevitable variability in clinical settings of different countries should be judiciously considered. Finally, only the literatures published in English language were considered for eligibility of this meta-analysis. We would identify more additional literatures if removing the language limitation.


 » Discussion Top


This meta-analysis shows no significant differences in the rate of survival and disease-free survival between PCT-S group and surgery (S) alone group. Although a previous study suggest that PCT may improve survival.[9] It may be related to the small sample size. However, the speculation still needs further tests to verify. There are no significant differences in intra- and post-operative complication rates, such as neutropenia, thrombocytopenia, bronchial fistula, pulmonary embolism, nausea and vomiting, respiratory failure, etc., however, due to limited quality and quantity of the included studies. These conclusions should be received cautiously. In addition, not all included studies were detected publication bias.

Anyway, this meta-analysis indicated that PCT-S application can reduce recurrence rate. As is well known that recurrence rate is an independent risk factor for NSCLC prognosis. Although no significance between PCT and survival rate, incidence of complications was found in this meta-analysis. We believe in positive discovery, if more rigorously randomized controlled trials would be performed. Meanwhile, this study lack a further study of different PCT. What's more, not all PCT can reduce the recurrence rate in this study. Hence, further studies should be conducted to investigate the safety and efficacy between different PCT on a broader scale.


 » Conclusions Top


In this meta-analysis, whereas PCT performed lower recurrence rate, disease-free and overall survivals remain the gold-standard for evaluation of efficacy, there are significant differences between two groups in the overall survival rate and disease-free survival rate. In terms of safety, PCT show no advantages. Therefore, we may re-estimate of the effectiveness and safety of new therapies and the updated high-quality studies can help to further confirm and enrich our discoveries in the future.

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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