|Year : 2017 | Volume
| Issue : 1 | Page : 223-227
The efficacy and safety of preoperative chemotherapy for patients with nonsmall cell lung cancer: A meta-analysis
T Wang, T Yan, S Ma, K Wang, J Wang, J Song, W He, J Bai, L Jin
Department of Thoracic Surgery, Peking University Third Hospital, Beijing 100191, China
|Date of Web Publication||1-Dec-2017|
Dr. T Yan
Department of Thoracic Surgery, Peking University Third Hospital, Beijing 100191
Source of Support: None, Conflict of Interest: None
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 2021 Aug 1];54:223-7. Available from: https://www.indianjcancer.com/text.asp?2017/54/1/223/219598
| » Introduction|| |
Lung cancer is the leading cause of cancer-related death in most countries of the world., 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%.
There are different standards for NSCLC treatment. In general, surgical resection is the first choice to treat lung cancer., 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., 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., Thus, PCT, with or without resection (preferably lobectomy), is an option for patients.
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.,,, 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|| |
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.
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.
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|| |
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 ,,,,,,,,,, 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).
Relevant efficacy indicators analysis between preoperative chemotherapy plus surgery group and S group
Nine studies ,,,,,,,, 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 ,,,,,, 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 ,, 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 ,,,,, 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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Relevant safety indicators analysis between preoperative chemotherapy plus surgery group and S group
Five Researches ,,,, 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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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|| |
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. 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|| |
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
Conflicts of interest
There are no conflicts of interest.
| » References|| |
Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, et al.
Cancer incidence and mortality patterns in Europe: Estimates for 40 countries in 2012. Eur J Cancer 2013;49:1374-403.
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin 2012;62:10-29.
Nguyen KS, Neal JW, Wakelee H. Review of the current targeted therapies for non-small-cell lung cancer. World J Clin Oncol 2014;5:576-87.
Coit DG, Thompson JA, Algazi A, Andtbacka R, Bichakjian CK, Carson WE 3rd
, et al.
Melanoma, Version 2.2016, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 2016;14:450-73.
Chang JY, Jabbour SK, De Ruysscher D, Schild SE, Simone CB 2nd
, Rengan R, et al.
Consensus statement on proton therapy in early-stage and locally advanced non-small cell lung cancer. Int J Radiat Oncol Biol Phys 2016;95:505-16.
Shepherd FA. Screening, diagnosis, and staging of lung cancer. Curr Opin Oncol 1993;5:310-22.
Gloeckler Ries LA, Reichman ME, Lewis DR, Hankey BF, Edwards BK. Cancer survival and incidence from the surveillance, epidemiology, and end results (SEER) program. Oncologist 2003;8:541-52.
Rosell R, Gómez-Codina J, Camps C, Javier Sánchez J, Maestre J, Padilla J, et al.
Preresectional chemotherapy in stage IIIA non-small-cell lung cancer: A 7-year assessment of a randomized controlled trial. Lung Cancer 1999;26:7-14.
Rosell R, Gómez-Codina J, Camps C, Maestre J, Padille J, Cantó A, et al.
Arandomized trial comparing preoperative chemotherapy plus surgery with surgery alone in patients with non-small-cell lung cancer. N
Engl J Med 1994;330:153-8.
Goldie JH, Coldman AJ. A mathematic model for relating the drug sensitivity of tumors to their spontaneous mutation rate. Cancer Treat Rep 1979;63:1727-33.
Depierre A, Milleron B, Moro-Sibilot D, Chevret S, Quoix E, Lebeau B, et al.
Preoperative chemotherapy followed by surgery compared with primary surgery in resectable stage I (except T1N0), II, and IIIa non-small-cell lung cancer. J Clin Oncol 2002;20:247-53.
Gilligan D, Nicolson M, Smith I, Groen H, Dalesio O, Goldstraw P, et al.
Preoperative chemotherapy in patients with resectable non-small cell lung cancer: Results of the MRC LU22/NVALT 2/EORTC 08012 multicentre randomised trial and update of systematic review. Lancet 2007;369:1929-37.
Scagliotti GV, Pastorino U, Vansteenkiste JF, Spaggiari L, Facciolo F, Orlowski T, et al
. A phase III randomized study of surgery alone or surgery plus preoperative gemcitabine-cisplatin in early-stage non-small cell lung cancer (NSCLC): Follow-up data of Ch.ES. J Clin Oncol 2008;26:431-6.
Sorensen JB, Riska H, Ravn J, Hansen O, Palshof T, Rytter C, et al
. Scandinavian phase III trial of neoadjuvant chemotherapy in NSCLC stages IB-IIIA/T3. J Clin Oncol 2005;23:656S.
Zhou Q, Liu L, Li L, Che G, Yang J, Zhao Y, et al.
Arandomized clinical trial of preoperative neoadjuvant chemotherapy followed by surgery in the treatment of stage III non-small cell lung cancer. Zhongguo Fei Ai Za Zhi 2001;4:251-6.
Scagliotti GV, Pastorino U, Vansteenkiste JF, Spaggiari L, Facciolo F, Orlowski TM, et al.
Randomized phase III study of surgery alone or surgery plus preoperative cisplatin and gemcitabine in stages IB to IIIA non-small-cell lung cancer. J Clin Oncol 2012;30:172-8.
Roth JA, Fossella F, Komaki R, Ryan MB, Putnam JB Jr., Lee JS, et al.
Arandomized trial comparing perioperative chemotherapy and surgery with surgery alone in resectable stage IIIA non-small-cell lung cancer. J Natl Cancer Inst 1994;86:673-80.
Pisters KM, Vallières E, Crowley JJ, Franklin WA, Bunn PA Jr., Ginsberg RJ, et al.
Surgery with or without preoperative paclitaxel and carboplatin in early-stage non-small-cell lung cancer: Southwest oncology group trial S9900, an intergroup, randomized, phase III trial. J Clin Oncol 2010;28:1843-9.
Nagai K, Tsuchiya R, Mori T, Tada H, Ichinose Y, Koike T, et al.
Arandomized trial comparing induction chemotherapy followed by surgery with surgery alone for patients with stage IIIA N2 non-small cell lung cancer (JCOG 9209). J Thorac Cardiovasc Surg 2003;125:254-60.
Liao ML, Zhou YZ, Ding JA, Ni GX, Zhao JM, Chen WH, et al.
The study of peri-operative chemotherapy in stage I-IIIa NSCLC. Zhonghua Yi Xue Za Zhi 2003 10;83:962-6.
Li Q, Song YH, Zheng ZY, Han YT, Peng L, Xiao B,et al
. Clinical evaluation of preoperative short-course chemotherapy in treatment of stage non-small cell lung cancer. China J Cancer Prev Treat 2003;10:505-7.
Felip E, Rosell R, Maestre JA, Rodríguez-Paniagua JM, Morán T, Astudillo J, et al.
Preoperative chemotherapy plus surgery versus surgery plus adjuvant chemotherapy versus surgery alone in early-stage non-small-cell lung cancer. J Clin Oncol 2010;28:3138-45.
Dautzenberg B, Benichou J, Allard P, Lebeau B, Coetmeur D, Brechot JM, et al.
Failure of the perioperative PCV neoadjuvant polychemotherapy in resectable bronchogenic non-small cell carcinoma. Results from a randomized phase II trial. Cancer 1990;65:2435-41.
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