Oncology

doi: 10.25005/2074-0581-2019-21-3-420-425
COMBINED TREATMENT OF PATIENTS WITH NON-SMALL CELL LUNG CANCER WITH PERSONALIZED PRESCRIPTION OF ADJUVANT CHEMOTHERAPY

E.O. Rodionov1,2, S.V. Miller1, L.A. Efteev1, S.A. Tuzikov1,2, M.M. Tsyganov3, I.V. Deryusheva3, N.V. Litvyakov3,4, V.A. Markovich1, U.B. Urmonov5

1Department of Thoracic Oncology, Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, Russian Federation
2Department of Oncology, Siberian State Medical University, Tomsk, Russian Federation
3Oncovirology Laboratory, Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, Russian Federation
4Institute of Biology, Ecology, Soil Science, Agriculture and Forestry, National Research Tomsk State University, Tomsk, Russian Federation
5Department of Abdominal Oncology, Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, Russian Federation

Objective: To study the long-term results of the combined treatment of non-small cell lung cancer (NSCLC) using pre-surgery chemotherapy, radical surgery and personalized adjuvant chemotherapy based on the level of monoresistance genes.

Methods: Four-year results of treatment of 72 patients of NSCLC II-III stage were analyzed. All patients underwent 2 courses of neoadjuvant chemotherapy (vinorelbine/carboplatin) and surgical treatment. Personalized adjuvant chemotherapy based on the levels of expression of monoresistance genes АВСС5, RRM1, TYMS, TOP1, TOP2α, TUBB3, BRCA1, and ERCC1 was performed in the main group (n=35). Three courses of adjuvant chemotherapy (vinorelbine/carboplatin) were performed in the control group (n=37).

Results: In the main group the progression of the disease was observed in 14 out of 35, and in the control group – in 21 out of 37 patients. Relapsefree survival (RFS) in the main group was 60.0% (95% CI: 43.6-74.5), in the control group – 43.2% (95% CI: 28.7-59.1); Log-Rank test χ2 =3,071, р=0,080; RR=1,808 (95% CI: 0.918-3.561). The median RFS in the control group was 27 months (95% CI: 5.7-48.3). The overall survival rate in the main group was 77.1% (95% CI: 61.0-87.9), in the control group – 54.1% (95% CI: 38.4-69.0); Log-Rank test χ2 =2,813, p=0.094; RR=2,024 (95% CI: 0,870-4,709).

Conclusions: The developed method of personalized prescribing adjuvant chemotherapy to patients with NSCLC based on the molecular genetic characteristics of the tumor improves relapse-free and overall survival.

Keywords: Non-small cell lung cancer , monoresistance genes , personalized chemotherapy.

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References
  1. Choynzonov EL, Zhuykova LD, Ananina AO, Polishchuk TV, Pikalova LV. Vyzhivaemost’ bol’nykh rakom lyogkogo na territorii Tomskoy oblasti (2004-2013) [Survival of lung cancer patients residing in Tomsk region (2004-2013)]. Sibirskiy onkologicheskiy zhurnal. 2017;16(4):5-10. Available from: https://doi. org/10.21294/1814-4861-2017-16-4-5-10.
  2. Zukov RA, Modestov AA, Safontsev IP, Slepov EV, Narkevich AN. Otsenka mediko-demograficheskikh i ekonomicheskikh poter’ regiona, obuslovlennykh smertnost’yu ot raka lyogkogo [The evaluation of medical demographic and economic losses of the region conditioned by mortality of lung cancer]. Problemy sotsial’noy gigieny, zdravookhraneniya i istorii meditsiny. 2017;25(6):332-5. Available from: https://doi.org/10.32687/0869- 866X-2017-25-6-332-335.
  3. Choynzonov EL, Pisareva LF, Zhuykova LD, Ananina OA, Odintsova IN. Zabolevaemost’ zlokachestvennymi novoobrazovaniyami organov dykhaniya v Tomskoy oblasti (2005-2016) [Incidence of respiratory system cancer in the Tomsk region (2005-2016)]. Voprosy onkologii. 2018;64(6):732-8.
  4. GLOBOCAN. URL: http://globocan.iarc.fr/old/pie/Accessed April 15, 2019.
  5. Postmus PE, Kerr KM, Oudkerk M, Senan S, Waller DA, Vansteenkiste J, et al. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28(Suppl 4):iv1-iv21. Available from: https://doi.org/10.1093/annonc/ mdx222.
  6. Varela G, Thomas PA. Surgical management of advanced non-small cell lung cancer. J Thorac Dis. 2014;6(Suppl 2):S217-S223. Available from: https://doi. org/10.3978/j.issn.2072-1439.2014.04.34.
  7. Yumov ЕL, Miller SV, Litvyakov NV, Polishchuk ТV, Tuzikov SА, Cheremisina ОV, i dr. Khimioterapiya v kombinirovannom lechenii mestnorasprostranyonnogo nemelkokletochnogo raka lyogkogo [Chemotherapy in combined modality treatment for locally advanced non-small cell lung cancer]. Sibirskiy onkologicheskiy zhurnal. 2014;2:9-13.
  8. Pirker R, Filipits M. Adjuvant therapy in patients with completely resected non-small-cell lung cancer: current status and perspectives. Clin Lung Cancer. 2019;20(1):1-6. Available from: https://doi.org/10.1016/J.CLLC.2018.09.016.
  9. NSCLC Meta-analysis Collaborative Group. Preoperative chemotherapy for non-small-cell lung cancer: a systematic review and meta-analysis of individual participant data. Lancet. 2014;383(9928):1561-71. Available from: https://doi.org/10.1016/S0140-6736(13)62159-5.
  10. NSCLC Meta-analyses Collaborative Group, Arriagada R, Auperin A, Burdett S, Higgins JP, Johnson DH, Le Chevalier T, Le Pechoux C, Parmar MK, Pignon JP, Souhami RL, Stephens RJ, Stewart LA, Tierney JF, Tribodet H, van Meerbeeck J. Adjuvant chemotherapy, with or without postoperative radiotherapy, in operable non-small-cell lung cancer: two meta-analyses of individual patient data. Lancet. 2010;375(9722):1267-77. Available from: https://doi. org/10.1016/S0140-6736(10)60059-1.
  11. Huang ZL, Cao X, Luo RZ, Chen YF, Zhu LC, Wen Z. Analysis of ERCC1, BRCA1, RRM1 and TUBB3 as predictors of prognosis in patients with non-small cell lung cancer who received cisplatin-based adjuvant chemotherapy: A prospective study. Oncol Lett. 2015;11(1):299-305. Available from: https://doi. org/10.3892/ol.2015.3894.
  12. Kim ES. Chemotherapy resistance in lung cancer. Adv Exp Med Biol. 2016;893:189-209. Available from: https://doi.org/10.1007/978-3-319- 24223-1_10.
  13. Olaussen KA, Postel-Vinay S. Predictors of chemotherapy efficacy in nonsmall-cell lung cancer: a challenging landscape. Ann Oncol. 2016;27(11):2004- 16. Available from: https://doi.org/10.1093/annonc/mdw321.
  14. Tsyganov MM, Rodionov EO, Deryusheva IV, Miller SV, Ibragimova MK, Pisareva LF, i dr. Otsenka prognosticheskoy znachimosti ekspressii genov monorezistentnosti v opukholi bol’nykh nemelkokletochnym rakom lyogkogo posle predoperatsionnoy khimioterapii [Prognostic significance of monoresistance gene expression in tumors of patients with non-small cell lung cancer after preoperative chemotherapy]. Voprosy onkologii. 2017;63(1):122-7.

Authors informations:

Rodionov Evgeniy Olegovich Candidate of Medical Sciences, Senior Researcher, Department of Thoracic Oncology, Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences; Assistant, Department of Oncology, Siberian State Medical University SCOPUS: 57189622130 Researcher ID: B-7280-2017 ORCID ID: 0000-0003-4980-8986 Author ID: 805452 SPIN: 7650-2129 E-mail: rodionov_eo@oncology.tomsk.ru

Miller Sergey Viktorovich Doctor of Medical Sciences, Leading Researcher, Department of Thoracic Oncology, Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences SCOPUS: 56525429400 Researcher ID: C-8970-2012 ORCID ID: 0000-0002-5365-9840 SPIN: 6510-9849 Author ID: 558789 E-mail: miller_sv@sibmail.com

Efteev Leonid Aleksandrovich Junior Researcher, Department of Thoracic Oncology, Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences ORCID ID: 0000-0002-9054-0742 SPIN: 3474-4654 E-mail: efteyco@rambler.ru

Tuzikov Sergey Aleksandrovich Doctor of Medical Sciences, Full Professor, Head of the Department of Thoracic Oncology, Cancer Research Institute, Tomsk National Research Medical Center Russian Academy of Sciences; Professor of the Department of Oncology, Siberian State Medical University SCOPUS: 6507842873 Researcher ID: D-1176-2012 ORCID ID: 0000-0002-0884-1838 Author ID: 455003 SPIN: 5662-6431 E-mail: TuzikovSA@oncology.tomsk.ru

Tsyganov Matvey Mikhaylovich Candidate of Biological Sciences, Senior Researcher, Oncovirology Laboratory, Cancer Research Institute, Tomsk National Medical Research Center of the Russian Academy of Sciences SCOPUS: 55366377400 Researcher ID: A-7212-2014 ORCID ID: 0000-0001-7419-4512 SPIN: 1253-0240 E-mail: TsyganovMM@yandex.ru

Deryusheva Irina Valeryevna Junior Researcher, Oncovirology Laboratory, Cancer Research Institute, Tomsk National Medical Center of the Russian Academy of Sciences Scopus: 57194535404 Researcher ID: q-5607-2017 ORCID ID: 0000-0002-9568-3371 SPIN: 5560-6131 E-mail: Irkin_097@mail.ru

Litvyakov Nikolay Vasilyevich Doctor of Biological Sciences, Head of the Oncovirology Laboratory, Cancer Research Institute, Tomsk National Medical Center of Russia Academy of Sciences; Senior Researcher, National Research Tomsk State University SCOPUS: 6506850698 Researcher ID: C-3263-2012 ORCID ID: 0000-0002-0714-8927 SPIN: 2546-0181 E-mail: nvlitv72@yandex.ru

Markovich Vitaliy Aleksandrovich Junior Researcher, Department of Thoracic Oncology, Cancer Research Institute, Tomsk National Research Medical Center of Russian Academy of Sciences ORCID ID: 0000-0002-7599-1211 SPIN: 2954-8330 Author ID: 968514 E-mail: vitalii.markovich.87@mail.ru

Urmonov Umidzhon Butabekovich Postgraduate Student, Department of Abdominal Oncology, Cancer Research Institute, Tomsk National Research Medical Center of Russian Academy of Sciences ORCID ID: 0000-0003-2804-4227 SPIN: 7150-7291 E-mail: Urmonovub@oncology.tomsk.ru

Address for correspondence:

Rodionov Evgeniy Olegovich
Candidate of Medical Sciences, Senior Researcher, Department of Thoracic Oncology, Cancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences; Assistant, Department of Oncology, Siberian State Medical University

634009, Russian Federation, Tomsk, lane Kooperativniy, 5

Tel.: +7 (952) 8894663

E-mail: rodionov_eo@oncology.tomsk.ru

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