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Efficacy of early combination of local radiotherapy and GM-CSF for advanced non-small cell lung cancer treated with icotinib



Lung cancer is a disease that severely endangers human health. Non-small cell lung cancer (NSCLC) accounts for approximately 4/5 of lung cancers.


To investigate the efficacy of early combination of local radiotherapy and granulocyte macrophage colony-stimulating factor (GM-CSF) for advanced NSCLC treated with icotinib.


Forty-two patients with stage IV NSCLC complicated with EGFR gene mutation were selected and randomly divided into two groups, with 21 patients in each group. Patients in control group were treated with icotinib, and patients in experimental group were treated with icotinib combined with local radiotherapy and subcutaneous injection of GM-CSF. One-year progression free survival between two groups was compared.


Three months after treatment, the efficacy in experimental group was significantly better than that in control group, and objective response rate was 95.24% in experimental group, which was higher than the 71.43% in control group. Patients in experimental group had no differences in white blood cell and neutrophil, but had significantly lower carcino-embryonic antigen and neuron-specific enolase levels and higher CD3+, CD4+, and CD4+/CD8+ than those in control group and before treatment. There were no differences in the proportion of patients with adverse reactions between two groups. One-year progression free survival was significantly better in experimental group than in control group.


Early combination of local radiotherapy and GM-CSF has a significant efficacy for advanced NSCLC accounts for approximately 4/5 of lung cancers treated with icotinib, and it can improve patients’ autoimmunity and lengthen progression free survival.

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  1. Leal TA, Ramalingam SS (2018) Immunotherapy in previously treated non-small cell lung cancer (NSCLC). J Thorac Dis 10:S422–Ss32.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Rotow J, Bivona TG (2017) Understanding and targeting resistance mechanisms in NSCLC. Nat Rev Cancer 17:637–658.

    Article  CAS  PubMed  Google Scholar 

  3. Russo A, Franchina T, Ricciardi GRR, Smiroldo V, Picciotto M, Zanghi M et al (2017) Third generation EGFR TKIs in EGFR-mutated NSCLC: where are we now and where are we going. Crit Rev Oncol Hematol 117:38–47.

    Article  CAS  PubMed  Google Scholar 

  4. Lee DH (2017) Treatments for EGFR-mutant non-small cell lung cancer (NSCLC): the road to a success, paved with failures. Pharmacol Ther 174:1–21.

    Article  CAS  PubMed  Google Scholar 

  5. Ghafoor Q, Baijal S, Taniere P, O'Sullivan B, Evans M, Middleton G (2018) Epidermal growth factor receptor (EGFR) kinase inhibitors and non-small cell lung cancer (NSCLC)-advances in molecular diagnostic techniques to facilitate targeted therapy. Pathol Oncol Res 24:723–731.

    Article  CAS  PubMed  Google Scholar 

  6. Bruckl W, Tufman A, Huber RM (2017) Advanced non-small cell lung cancer (NSCLC) with activating EGFR mutations: first-line treatment with afatinib and other EGFR TKIs. Expert Rev Anticancer Ther 17:143–155.

    Article  CAS  PubMed  Google Scholar 

  7. Leduc C, Merlio JP, Besse B, Blons H, Debieuvre D, Bringuier PP et al (2017) Clinical and molecular characteristics of non-small-cell lung cancer (NSCLC) harboring EGFR mutation: results of the nationwide French Cooperative Thoracic Intergroup (IFCT) program. Ann Oncol 28:2715–2724

    Article  CAS  Google Scholar 

  8. Zou B, Lee VHF, Yan H (2018) Prediction of sensitivity to gefitinib/erlotinib for EGFR mutations in NSCLC based on structural interaction fingerprints and multilinear principal component analysis. BMC Bioinforma 19:88.

    Article  CAS  Google Scholar 

  9. Goto Y, Tanai C, Yoh K, Hosomi Y, Sakai H, Kato T et al (2017) Continuing EGFR-TKI beyond radiological progression in patients with advanced or recurrent, EGFR mutation-positive non-small-cell lung cancer: an observational study. ESMO open 2:e000214

    Article  Google Scholar 

  10. Crittenden M, Kohrt H, Levy R, Jones J, Camphausen K, Dicker A, Demaria S, Formenti S (2015) Current clinical trials testing combinations of immunotherapy and radiation. Semin Radiat Oncol 25:54–64.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Harrington KJ, Hingorani M, Tanay MA, Hickey J, Bhide SA, Clarke PM, Renouf LC, Thway K, Sibtain A, McNeish I, Newbold KL, Goldsweig H, Coffin R, Nutting CM (2010) Phase I/II study of oncolytic HSV GM-CSF in combination with radiotherapy and cisplatin in untreated stage III/IV squamous cell cancer of the head and neck. Clin Cancer Res 16:4005–4015

    Article  CAS  Google Scholar 

  12. Liang XT, Wu J (2016) Application of ECOG rating scale in graded nursing of patients with lung cancer chemotherapy. J Prey Med Chin PLA 34:125–126

    CAS  Google Scholar 

  13. Guenther LM, Rowe RG, Acharya PT, Swenson DW, Meyer SC, Clinton CM, et al (2018) Response evaluation criteria in solid tumors (RECIST) following neoadjuvant chemotherapy in osteosarcoma. Pediatr Blood Cancer 65.

  14. Ma HL, Zhang HT (2014) Effect of chemotherapy combined with traditional Chinese medicine on immune function and KPS score in patients with advanced non-small cell lung cancer. Hainan Med J 2014:2271–2272

    Google Scholar 

  15. Chen DF, Sun WJ, Xiong J (2012) The diagnosis and treatment of drug-induced liver injury. Chin J Hepatol 20:170–172.

    Article  CAS  Google Scholar 

  16. Dai Y (2012) Clinical observation of Yifei Jiedu decoction combined with PP regimen in the treatment of advanced non-small cell lung cancer: Nanjing University of traditional Chinese medicine 2012

  17. Lakshmi SP, Reddy AT, Banno A, Reddy RC (2017) PPAR agonists for the prevention and treatment of lung cancer. PPAR Res 2017:8252796.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Sharma AVB, Park YS (2018) Role of probiotics in the management of lung cancer and related diseases: an update. J Funct Foods 40:625–633.

    Article  Google Scholar 

  19. Chang CH, Lee CH, Ko JC, Chang LY, Lee MC, Wang JY, Yu CJ (2017) Gefitinib or erlotinib in previously treated non-small-cell lung cancer patients: a cohort study in Taiwan. Cancer Med 6:1563–1572.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Zhou J, Song XB, He H, Zhou Y, Lu XJ, Ying BW (2016) Prevalence and clinical profile of EGFR mutation in non-small-cell lung carcinoma patients in Southwest China. Asian Pac J Cancer Prev 17:965–971.

    Article  PubMed  Google Scholar 

  21. Yang Z, Tam KY (2018) Combination strategies using EGFR-TKi in NSCLC therapy: learning from the gap between pre-clinical results and clinical outcomes. Int J Biol Sci 14:204–216.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Liu HL (2016) Clinical observation of pemetrexed monotherapy or combined with gefitinib in the treatment of advanced lung adenocarcinoma after EGFR-TKI resistance: Zhengzhou University 2016

  23. Xia GH, Zeng Y, Fang Y, Yu SR, Wang L, Shi MQ et al (2014) Effect of EGFR-TKI retreatment following chemotherapy for advanced non-small cell lung cancer patients who underwent EGFR-TKI. Cancer Biol Med 11:270–276

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Huang CY, Ju DT, Chang CF, Muralidhar Reddy P, Velmurugan BK (2017) A review on the effects of current chemotherapy drugs and natural agents in treating non-small cell lung cancer. Biomedicine (Taipei) 7:23.

    Article  Google Scholar 

  25. Nebiker CA, Han J, Eppenberger-Castori S, Iezzi G, Hirt C, Amicarella F, Cremonesi E, Huber X, Padovan E, Angrisani B, Droeser RA, Rosso R, Bolli M, Oertli D, von Holzen U, Adamina M, Muraro MG, Mengus C, Zajac P, Sconocchia G, Zuber M, Tornillo L, Terracciano L, Spagnoli GC (2014) GM-CSF production by tumor cells is associated with improved survival in colorectal cancer. Clin Cancer Res 20:3094–3106.

    Article  CAS  PubMed  Google Scholar 

  26. Golden EB, Chhabra A, Chachoua A, Adams S, Donach M, Fenton-Kerimian M, Friedman K, Ponzo F, Babb JS, Goldberg J, Demaria S, Formenti SC (2015) Local radiotherapy and granulocyte-macrophage colony-stimulating factor to generate abscopal responses in patients with metastatic solid tumours: a proof-of-principle trial. Lancet Oncol 16:795–803.

    Article  CAS  PubMed  Google Scholar 

  27. Chang CC, Chi KH, Kao SJ, Hsu PS, Tsang YW, Chang HJ, Yeh YW, Hsieh YS, Jiang JS (2011) Upfront gefitinib/erlotinib treatment followed by concomitant radiotherapy for advanced lung cancer: a mono-institutional experience. Lung Cancer 73:189–194.

    Article  PubMed  Google Scholar 

  28. Deng G, Hu P, Zhang J, Liu Q, Liang N, Xie J et al (2016) Elevated serum granulocyte-macrophage colony-stimulating factor levels during radiotherapy predict favorable outcomes in lung and esophageal cancer. Oncotarget 7:85142–85150.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Anguille S, Smits EL, Lion E, van Tendeloo VF, Berneman ZN (2014) Clinical use of dendritic cells for cancer therapy. Lancet Oncol 15:e257–e267.

    Article  CAS  PubMed  Google Scholar 

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This work was supported by the Research Project of the Health and Family Planning Commission of Yibin (2018yw011).

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Correspondence to Yuming Jia.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Ye Qiu and Xinyun He are Co-first authors

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Qiu, Y., He, X., Li, Z. et al. Efficacy of early combination of local radiotherapy and GM-CSF for advanced non-small cell lung cancer treated with icotinib. Ir J Med Sci 189, 791–797 (2020).

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  • Non-small cell lung cancer
  • Icotinib
  • Local radiotherapy
  • Tumor markers
  • Immune indexes