Postoperative UFT-/Tegafur-based Chemotherapy Versus Postoperative Radiotherapy for Early-stage Non-small Cell Lung Cancer：A Systematic Review and Network Meta-analysis

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DOI: https://doi.org/10.30564/jor.v1i2.1493

Abstract:

Background: Both of UFT-/Tegafur-based postoperative chemotherapy and postoperative radiotherapy have made large progress in treatment of early-stage non-small cell lung cancer. While it is unclear that, whether UFT-/Tegafur-based postoperative chemotherapy is superior to postoperative radiotherapy for early-stage non-small cell lung cancer with no direct evidence. Methods: Electronic databases (Pubmed, embase, cochrane library and clinicaltrials.gov) were searched to obtain relevant studies. This systematic review and meta-analysis is reported in accordance with the Preferred Items for Systematic Reviews and Meta-analysis (PRISMA) Statement and was registered at International Prospective Register of Systematic Reviews (number CRD42018095979). Sensitive analysis was conducted by excluding overweight studies. Funnel plot and egger’s test were performed to conduct publication bias. Results: Twenty-one randomized control trials were included. Our results suggested UFT-/Tegafur-based postoperative chemotherapy could improve overall survival over postoperative radiotherapy [HR=0.69 (0.59-0.80), p=0.000]. But subgroup analysis about stage showed there was no significant difference between them, no matter of stageⅠ,Ⅱ and Ⅲ. As to chemotherapy regime, both UFT-/Tegafur + platinum+vinca alkaloid [HR=0.68 (0.56-0.82), p=0.000] and UFT-/Tegafur only [HR=0.66 (0.54-0.79), p=0.000] were superior to radiotherapy. Subgroup analysis about radiotherapy delivery method and dose showed, significant improvement of chemotherapy over radiotherapy for Cobalt-60 only [HR=0.54 (0.39-0.75), p=0.000], Cobalt-60 and linac [HR=0.69 (0.59-0.81), p=0.000] and ≥45 Gy [HR=0.64 (0.54-0.75), p=0.000], but not for linac only [HR=0.78 (0.60-1.03), p=0.081] and ＜45 Gy [HR=0.86 (0.67-1.11), p=0.241]. Conclusion: UFT-/Tegafur-based postoperative chemotherapy was superior to postoperative radiotherapy for improving overall survival of early-stage non-small cell lung cancer, but it is not always so under certain circumstance, such as RT delivery method and radiation dose. Of course, it is imperative to further explore differences in specific stage, such as ⅠA and ⅠB.

References:

[1]American Cancer Society. Cancer Facts and Figures 2007. Atlanta: American Cancer Society, 2007. [2]Mountain, Clifton F. Revisions in the International System for Staging Lung Cancer. Chest, 1997, 111(6): 1710-1717. [3]Naruke T, Tsuchiya R, Kondo H, et al. Implications of Staging in Lung Cancer. Chest, 1997, 112(4): 242S-248S. [4]Hotta K, Matsuo K, Ueoka H, et al. Role of Adjuvant Chemotherapy in Patients With Resected Non–Small-Cell Lung Cancer: Reappraisal With a Meta-Analysis of Randomized Controlled Trials. Journal of Clinical Oncology Official Journal of the American Society of Clinical Oncology, 2004, 22(19): 3860. [5]Bin X, Yuan-Yuan C, Lin-Wei W, et al. Meta-analysis of postoperative adjuvant chemotherapy without radiotherapy in early stage non-small cell lung cancer. OncoTargets and Therapy, 2015: 2033-2043. [6]Hamada C, Tsuboi M, Ohta M, et al. Effect of Postoperative Adjuvant Chemotherapy with Tegafur-Uracil on Survival in Patients with Stage IA Non-small Cell Lung Cancer: An Exploratory Analysis from a Meta-Analysis of Six Randomized Controlled Trials. Journal of Thoracic Oncology, 2009, 4(12): 1511-1516. [7]PORT Meta-analysis Trialists Group. Postoperative radiotherapy for non-small cell lung cancer. The Cochrane Database of Systematic Reviews, Issue. Art. No.: CD002142. DOI: 10.1002/14651858.CD002142 [8]PORT Meta-analysis Trialists Group. Postoperative radiotherapy for non-small cell lung cancer. Cochrane Database of Systematic Reviews 2005(2). Art. No.: CD002142. DOI: 10.1002/14651858.CD002142.pub2 [9]Sakib N , Li N , Zhu X , et al. Effect of postoperative radiotherapy on outcome in resectable stage IIIA-N2 non-small-cell lung cancer: an updated meta-analysis. Nuclear Medicine Communications, 2018, 39(1):51-59. [10]Patel S H, Ma Y, Wernicke A G, et al. Evidence supporting contemporary post-operative radiation therapy (PORT) using linear accelerators in N2 lung cancer. Lung Cancer, 2014, 84(2): 156-160. [11]Glenny, A. M., Altman, D. G., Song, F., et al. Indirect comparisons of competing interventions. Health Technology Assessment, 2005, 9(26): 1. [12]Song, F., Altman, D. G., Glenny, A. M., et al. Validity of indirect comparison for estimating efficacy of competing interventions: empirical evidence from published meta-analyses. Bmj. 2003, 326(7387): 472. [13]Lim, E., Harris, G., Patel, A., et al. Preoperative versus postoperative chemotherapy in patients with resectable non-small cell lung cancer: systematic review and indirect comparison meta-analysis of randomized trials. Journal of Thoracic Oncology, 2009, 4(11): 1380-1388. [14]Biondizoccai, G., Lotrionte, M., Agostoni, P., et al. Adjusted indirect comparison meta-analysis of prasugrel versus ticagrelor for patients with acute coronary syndromes, International Journal of Cardiology. 2011, 150(3): 325-331. [15]Study Group for Adjuvant Chemotherapy for Lung Cancer. A randomised controlled trial of postoperative adjuvant chemotherapy in non-small cell lung cancer (in Japanese). Hai-gan, 1992, 32: 481–486. [16]Study Group for Adjuvant Chemotherapy for Lung Cancer. A randomized trial of postoperative adjuvant chemotherapy in non-small cell lung cancer (the second cooperative study). European Journal of Surgical Oncology, 1995, 21(1): 69–77. [17]Wada H, Hitomi S, Takashi T, West Japan Study Group for Lung Cancer Surgery. Adjuvant chemotherapy after complete resection in non-small cell lung cancer. Journal of Clinical Oncology, 1996(14): 1048–1054. [18]Wada H, Miyahara R, Tanaka F, et al, West Japan Study Group for Lung Cancer Surgery. Post-operative adjuvant chemotherapy with PVM (cisplatin + vindesine +mitomycin c) and UFT (uracil and tegaful) in resected stage I-II NSCLC (non-small cell lung cancer): a randomized clinical trial. European Journal of Cardio-Thoracic Surgery, 1999, 15: 438–443. [19]Xu G, Rong T, Lin P. Adjuvant chemotherapy following radical surgery for non-small cell lung cancer: a randomized study. Zhonghua Zhong Liu Za Zhi. 1998, 20(3): 228–230 [20]Imaizumi M. Postoperative adjuvant cisplatin, vindesine, plus uracil-tegafur chemotherapy increased survival of patients with completely resected p-stage I non-small cell lung cancer, Lung Cancer, 2005, 49: 85–94. [21]Nakagawa K, Tada H, Akash iA, et al. Randomised study of adjuvant chemotherapy for completely resected p stage I-IIIa non-small cell lung cancer, British Journal of Cancer, 2006, 95: 817–21. [22]Nakagawa M, Tanaka F, Tsubota N, et al. A randomised phase III trial of adjuvant chemotherapy with UFT for completely resected pathological stage I non-small cell lung cancer: the West Japan Study Group for Lung Cancer Surgery (WJSG) – the 4th study, Annals of Oncology, 2005, 16: 75–80. [23]Sawamura K, Mori T, Doi O, et al. A prospective randomized controlled study of the postoperative adjuvant therapy for non-small cell lung cancer, Lung Cancer, 1998, 4: A166. [24]Endo C, Saitoi Y, Iwanawi H, T, et al. A randomized trial of postoperative UFT in p stage I, II non-small cell lung cancer: North-East Japan Study Group for Lung Cancer Surgery, Lung Cancer, 2003, 40: 181–186. [25]Kato H, Ichinose Y, Ohta M, et al. A randomised trial of adjuvant chemotherapy with uracil-tegafur for adenocarcinoma of the lung, New England Journal of Medicine, 2004, 350(17): 1713–21. [26]Chang, J. Y., Senan, S., Paul, M. A., et al. Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials. Lancet Oncology, 2015, 16(6): 630-637. [27]Park JH. Postoperative adjuvant therapy for stage IIIa nonsmall cell lung cancer. Journal of Thoracic Oncology, 2007, 2(8 Suppl 4): S651. [28]EORTC 08861(unpublished). Phase III randomized trial of adjuvant radiotherapy vs no adjuvant therapy with completely resected non-small cell lung cancer. [29]van Houtte P, Rocmans P, Smets P, et al. .Postoperative radiation therapy in lung cancer: a controlled trial after resection of curative design, International Journal of Radiation, Oncology, Biology and Physics, 1980, 6: 983–986. [30]Feng QF, Wang M, Wang LJ, et al. A study of postoperative radiotherapy in patients with non-small cell lung cancer: a randomized trial, International Journal of Radiation Oncology, Biology, Physics, 2000, 47(4): 925–929. [31]Dautzenberg B, Arriagada R, Chammard AB, et al. for the Groupe d’Etude et de Traitement des Cancers Bronchiques. A controlled study of postoperative radiotherapy for patients with completely resected nonsmall cell lung carcinom. Cancer, 1999, 86(2): 265–273. [32]Lung Cancer Study Group. Effects of postoperative mediastinal radiation on completely resected stage II and stage III epidermoid cancer of the lung. New England Journal of Medicine, 1986, 315(22): 1377–1381. [33]Stephens RJ, Girling DJ, Bleehen NM, et al. The role of post-operative radiotherapy in non-small cell lung cancer: a multicentre randomized trial in patients with pathologically staged T1-2, N1-2, M0 disease. British Journal of Cancer, 1996, 74: 632–639. [34]Lafitte JJ, Ribet ME, Prévost BM, et al. Post-irradiation for T2 N0 M0 non-small cell carcinoma: a prospective randomized study. Annals of Thoracic Surgery, 1996, 62: 830–834. [35]Trodella L, Granone P, Valente S, et al. Adjuvant radiotherapy in non-small cell lung cancer with pathological stage I: definitive results of a phase III randomised trial. Radiotherapy and Oncology, 2002, 62: 11–19. [36]Chansky, K., Sculier, J. P., Crowley, J. J., et al. The international association for the study of lung cancer staging project: prognostic factors and pathologic tnm stage in surgically managed non-small cell lung cancer. Journal of Thoracic Oncology, 2010, 4(7): 792-801. [37] Hamada, C., Tanaka, F., Ohta, M., et al. Meta-analysis of postoperative adjuvant chemotherapy with tegafur-uracil in non–small-cell lung cancer. Journal of Clinical Oncology, 2005, 23(22): 4999-5006.