Abstract

Case Report

Non-smoking woman with adenocarcinoma of the lung, IV stage with ROS1 mutation and acquired thrombophilia

Immanuels Taivans*, Natalja Senterjakova, Viktors Kozirovskis, Gunta Strazda, Jurijs Nazarovs and Valentina Gordjusina

Published: 04 August, 2021 | Volume 5 - Issue 1 | Pages: 064-072

Despite the fact, that lung cancer is more common among older smoking men, however it may also develop among young women without a smoking anamnesis. We report here a history of a non-smoking woman, 40 years old, with a diagnosis of lung adenocarcinoma at IV stage. Despite the fact, the woman received three lines of palliative chemotherapy, the disease progressed. After the sample of the tumor was tested by genetic approach, ROS1 mutation was detected, and the patient was treated with a ROS1 inhibitor, Crizotinib. Sharp improvement was observed already after the first week of treatment. After one-month adenocarcinoma shrink, and specific supraclavicular lymph nodes disappeared. Unfortunately, due to problems with financing the treatment was stopped, after what the disease began to progress rapidly, and the patient died after a month due to brain metastasis. This case is noteworthy also because the patient was first diagnosed a thrombophilia with thrombi present in deep calf veins, left heart ventricle and lungs Adenocarcinoma was discovered occasionally when during video-assisted thoracoscopic surgery biopsy specimen was taken from suspicious mass in the lower lobe of the right lung. This story reminds us that lung carcinoma may start with a paraneoplastic syndrome, like thrombophilia as in this case and finding of adenocarcinoma of the lung in young, non-smoking persons is indicative for possible ROS1 gene mutation. In such cases early treatment with ROS1 protein-tyrosine kinase inhibitors should be started as soon as possible.

Read Full Article HTML DOI: 10.29328/journal.jprr.1001027 Cite this Article Read Full Article PDF

Keywords:

Adenocarcinoma of the lung; ROS1 mutation; Crizotinib; Acquired thrombophylia

References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021; 0: 1-41.
  2. Islami F, Torre L.A, Jemal A. Global trends of lung cancer mortality and smoking prevalence. Transl Lung Cancer Res. 2015; 4: 327-338. PubMed: https://pubmed.ncbi.nlm.nih.gov/26380174/
  3. Ridge CA, McErlean AM, Ginsberg MS. Epidemiology of lung cancer. Semin Intervent Radiol. 2013; 30: 93-98. PubMed: https://pubmed.ncbi.nlm.nih.gov/24436524/
  4. Barrera-Rodriguez R, Morales-Fuentes J. Lung cancer in women. Lung Cancer (Auckl). 2012; 3: 79–89. PubMed: https://pubmed.ncbi.nlm.nih.gov/28210127/
  5. Statistiskas dati par 2017. gadu. Onkoloģija. 2017. https://www.spkc.gov.lv/lv/statistikas-dati
  6. Davies KD, Doebele RC. Molecular Pathways: ROS1 Fusion Proteins in Cancer. Clin Cancer Res. 2013; 19: 4040–4045. PubMed: https://pubmed.ncbi.nlm.nih.gov/23719267/
  7. Bergethon K, Shaw AT, Ou SH I, Katayama R, Lovly CM, et al. ROS1 ROS1 rearrangements define a unique molecular class of lung cancers. 2012; 30: 863–870. PubMed: https://pubmed.ncbi.nlm.nih.gov/22215748/
  8. Marchetti A, Barberis M, Di Lorito A, Pace MV, Chiara MV, et al. ROS1 Gene Fusion in Advanced Lung Cancer in Women: A Systematic Analysis, Review of the Literature, and Diagnostic Algorithm. JCO Precision Oncol. 2017; 1.
  9. Bubendorf L, Büttner R, Al-Dayel F, Dietel M, Elmberger G, et al. Testing for ROS1 in non-small cell lung cancer: a review with recommendations. Virchows Arch. 2016; 469: 489–503. PubMed: https://pubmed.ncbi.nlm.nih.gov/27535289/
  10. Shu Y, Li H, Shang H, Chen J, Su X, et al. Identification of a Novel MPRIP-ROS1 Fusion and Clinical Efficacy of Crizotinib in an Advanced Lung Adenocarcinoma Patient: A Case Report. Onco Targets Ther. 2020; 13: 10387–10391. PubMed: https://pubmed.ncbi.nlm.nih.gov/33116618/
  11. Solomon B. Validating ROS1 rearrangements as a therapeutic target in non-small-cell lung cancer. J Clin Onco. 2015; 33: 972-974. PubMed: https://pubmed.ncbi.nlm.nih.gov/25667277/
  12. Jun HJ, Johnson H, Bronson RT, de Feraudy S, White F, et al. The oncogenic lung cancer fusion kinase CD74-ROS activates a novel invasiveness pathway through E-Syt1 phosphorylation. Cancer Res. 2012; 72: 3764-3774. PubMed: https://pubmed.ncbi.nlm.nih.gov/22659450/
  13. Sholl LM, Sun H, Butaney M, Zhang C, Lee C, et al. ROS1 immunohistochemistry for detection of ROS1-rearranged lung adenocarcinomas. Am J Surg Patho. 2013; 37: 1441-1449. PubMed: https://pubmed.ncbi.nlm.nih.gov/23887156/
  14. Shaw AT, Ou SHI, Bang YJ, Camidge DR, Dolomon SJ, et al. Crizotinib in ROS1-rearranged non-small-cell lung cancer. N Engl J Med. 2014; 371: 1963-1971. PubMed: https://pubmed.ncbi.nlm.nih.gov/25264305/
  15. Kumar A, Shanthi V, Ramanathan K. Structural and Functional Impact of G2032R Mutation in ROS1-A Theoretical Perspective. Asian J Pharmaceut Clin Res. 2017; 10: 339-344.
  16. Sculier JP, Fry W. Pathology of Lung Cancer. Malignant Tumors of the Lung. 2004; 8th ed. 39-55.
  17. Quaia E. Radiologic-pathologic correlations between intratumoral macroscopic and microscopic components in lung neoplasms. Congress ECR. 2006; c-186.
  18. Qian X, Fu M, Zheng J, Zhou J, Zhou J. Driver Genes Associated with the Incidence of Venous Thromboembolism in Patients With Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis. Front Oncol. 2021; 11: 680191. PubMed: https://pubmed.ncbi.nlm.nih.gov/33996610/
  19. Chiari R, Ricciuti B, Landi L,  Morelli AM,  Delmonte A, et al. ROS1-rearranged Non-small-cell Lung Cancer is Associated With a High Rate of Venous Thromboembolism: Analysis From a Phase II, Prospective, Multicenter, Two-arms Trial (METROS). 2020; 21:15-20. PubMed: https://pubmed.ncbi.nlm.nih.gov/31607443/
  20. Liu Y, Wang W, Wu F, Gao G, Xu J, et al. High discrepancy in thrombotic events in non-small cell lung cancer patients with different genomic alterations. Transl Lung Cancer Res. 2021; 10: 1512-1524. PubMed: https://pubmed.ncbi.nlm.nih.gov/33889526/
  21. Kanaji N, Watanabe N, Kita N, Bandoh S, Tadokoro A, et al. Paraneoplastic syndromes associated with lung cancer. World J Clin Oncol. 2014; 5: 197-223. PubMed: https://pubmed.ncbi.nlm.nih.gov/25114839/
  22. Marinho FC. de A, Takagaki TY. Hypercoagulability and lung cancer. J Bras Pneumol. 2008; 34: 312-322. PubMed: https://pubmed.ncbi.nlm.nih.gov/18545828/
  23. Falanga A. The Cancer-Thrombosis Connection. The Hematologist:ASH News & Reports. 2011; 8: 4-5.
  24. Boccaccio C, Comoglio PM. Genetic link between cancer and thrombosis. J Clin Oncol. 2009; 27: 4827-4833. PubMed: https://pubmed.ncbi.nlm.nih.gov/19738115/
  25. Blaukovitsch M, Hofer J, Hutarew G, Müllauer L, Ingrid SK, et al. ROS1 mutation and treatment with Crizotinib in a 30-yearv old Caucasian woman with stage IV non-small cell lung cancer/adenocarcinoma and complete remission. Thorac Cancer. 2014; 5: 455-459. PubMed: https://pubmed.ncbi.nlm.nih.gov/26767038/

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