Association of Pre-treatment Sarcopenia with Side Effects and Prognosis in Non-small Cell Lung Cancer Patients Receiving Erlotinib

OBJECTIVE We investigated the relationship of baseline sarcopenia with toxicities, treatment response, and survival in patients who had non-small cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) mutation and received erlotinib. METHODS Computed tomography images from PET/CT scans before erlotinib treatment were retrospectively as- sessed. Skeletal muscle index, calculated as skeletal muscle area at third lumbar vertebra level/square of height, was used to define sarcopenia with <52.4 cm 2/m2 for males and <38.5 cm 2/m2 for females. Cox hazard models were conducted to determine predictors of survival. RESULTS The study included 30 patients, and 11 (36.7%) were sarcopenic. All-grade and Grade 3 toxicities were more frequent in sarcopenic group, although it was statistically insignificant (81.8% vs. 63.2%, p=0.282 for all-grade, and 18.2% vs. 10.5%, p=0.552 for grade 3). Response rates were 63.6% in sar- copenic and 68.4% in non-sarcopenic patients (p=0.789). Median progression-free survival was 7.9 and 9.2 months in sarcopenic and non-sarcopenic cases, respectively (p=0.561). However, median overall survival (OS) of sarcopenic patients was significantly shorter than non-sarcopenic ones (11.8 vs. 30.2 months, p=0.023), and sarcopenia predicted OS independently in multivariate analysis (Hazard ratio=2.63, p=0.029). CONCLUSION Early recognition, treatment, and prevention of sarcopenia may improve long-term survival in EGFR- mutant NSCLC patients treated with first-line erlotinib.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68(6):394–424.
2. Boch C, Kollmeier J, Roth A, Stephan-Falkenau S, Misch D, Grüning W, et al. The frequency of EGFR and KRAS mutations in non-small cell lung cancer (NSCLC): routine screening data for central Europe from a cohort study. BMJ Open 2013;3(4):e002560.
3. Midha A, Dearden S, McCormack R. EGFR mutation incidence in non-small-cell lung cancer of adeno- carcinoma histology: a systematic review and global map by ethnicity (mutMapII). Am J Cancer Res 2015;5(9):2892–911.
4. Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non- small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol 2011;12(8):735–42.
5. Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 2012;13(3):239–46.
6. Wu YL, Planchard D, Lu S, Sun H, Yamamoto N, Kim DW, et al. Pan-Asian adapted Clinical Practice Guide- lines for the management of patients with metastatic non-small-cell lung cancer: a CSCO-ESMO initiative endorsed by JSMO, KSMO, MOS, SSO and TOS. Ann Oncol 2019;30(2):171–210.
7. Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyère O, Cederholm T, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing 2019;48(1):16–31.
8. Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 2011;12(5):489–95.
9. Bozzetti F. Forcing the vicious circle: sarcopenia in- creases toxicity, decreases response to chemother- apy and worsens with chemotherapy. Ann Oncol 2017;28(9):2107–18.
10. Shachar SS, Williams GR, Muss HB, Nishijima TF. Prognostic value of sarcopenia in adults with solid tu- mours: A meta-analysis and systematic review. Eur J Cancer 2016;57:58–67.
11. Icard P, Iannelli A, Lincet H, Alifano M. Sarcopenia in resected non-small cell lung cancer: let’s move to patient-directed strategies. J Thorac Dis 2018;10(Suppl 26):S3138–42.
12. Buentzel J, Heinz J, Bleckmann A, Bauer C, Röver C, Bohnenberger H, et al. Sarcopenia as Prognostic factor in lung cancer patients: a systematic review and meta- analysis. Anticancer Res 2019;39(9):4603–12.
13. Portal D, Hofstetter L, Eshed I, Dan-Lantsman C, Sella T, Urban D, et al. L3 skeletal muscle index (L3SMI) is a surrogate marker of sarcopenia and frailty in non- small cell lung cancer patients. Cancer Manag Res 2019;11:2579–88.
14. Prado CM, Lieffers JR, McCargar LJ, Reiman T, Sawyer MB, Martin L, et al. Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a popula- tion-based study. Lancet Oncol 2008;9(7):629–35.
15. Villaseñor A, Ballard-Barbash R, Baumgartner K, Baumgartner R, Bernstein L, McTiernan A, et al. Prevalence and prognostic effect of sarcopenia in breast cancer survivors: The HEAL Study. J Cancer Surviv 2012;6(4):398–406.
16. Köstek O, Demircan NC, Gökyer A, Küçükarda A, Sunal BS, Hacıoğlu MB, et al. Skeletal muscle loss during anti-EGFR combined chemotherapy regimens predicts poor prognosis in patients with RAS wild metastatic colorectal cancer. Clin and Transl Oncol 2019;21(11):1510–7.
17. Nishigori T, Tsunoda S, Obama K, Hisamori S, Hashimoto K, Itatani Y, et al. Optimal cutoff values of skeletal muscle index to define sarcopenia for predic- tion of survival in patients with advanced gastric can- cer. Ann Surg Oncol 2018;25(12):3596–603.
18. Kim EY, Lee HY, Kim KW, Lee JI, Kim YS, Choi WJ, et al. Preoperative computed tomography-deter- mined sarcopenia and postoperative outcome after surgery for non-small cell lung cancer. Scand J Surg 2018;107(3):244–51.
19. Kim EY, Kim YS, Park I, Ahn HK, Cho EK, Jeong YM, et al. Prognostic significance of CT-determined sar- copenia in patients with small-cell lung cancer. J Tho- rac Oncol 2015;10(12):1795–9.
20. Roch B, Coffy A, Jean-Baptiste S, Palaysi E, Daures JP, Pujol JL, et al. Cachexia - sarcopenia as a determi- nant of disease control rate and survival in non-small lung cancer patients receiving immune-checkpoint in- hibitors. Lung Cancer 2020;143:19–26.
21. Arrieta O, De la Torre-Vallejo M, López-Macías D, Orta D, Turcott J, Macedo-Pérez EO, et al. Nutritional status, body surface, and low lean body mass/body mass index are related to dose reduction and severe gastrointestinal toxicity induced by afatinib in patients with non-small cell lung cancer. Oncologist 2015;20(8):967–74.
22. Rossi S, Di Noia V, Tonetti L, Strippoli A, Basso M, Schinzari G, et al. Does sarcopenia affect outcome in patients with non-small-cell lung cancer harboring EGFR mutations? Future Oncol 2018;14(10):919–26.
23. Salazar-Degracia A, Granado-Martínez P, Millán- Sánchez A, Tang J, Pons-Carreto A, Barreiro E. Reduced lung cancer burden by selective immunomodulators elicits improvements in muscle proteolysis and strength in cachectic mice. J Cell Physiol 2019;234(10):18041–52.
24. Prado CM, Baracos VE, McCargar LJ, Reiman T, Mourtzakis M, Tonkin K, et al. Sarcopenia as a de- terminant of chemotherapy toxicity and time to tu- mor progression in metastatic breast cancer patients receiving capecitabine treatment. Clin Cancer Res 2009;15(8):2920–6.
25. Li J, Deng Y, Zhang M, Cheng Y, Zhao X, Ji Z. Prog- nostic value of radiologically determined sarcopenia prior to treatment in urologic tumors: A meta-analy- sis. Medicine (Baltimore) 2019;98(38):e17213.
26. Antoun S, Baracos VE, Birdsell L, Escudier B, Sawyer MB. Low body mass index and sarcopenia associated with dose-limiting toxicity of sorafenib in patients with renal cell carcinoma. Ann Oncol 2010;21(8):1594–8.
27. Huillard O, Mir O, Peyromaure M, Tlemsani C, Giroux J, Boudou-Rouquette P, et al. Sarcopenia and body mass index predict sunitinib-induced early dose- limiting toxicities in renal cancer patients. Br J Cancer 2013;108(5):1034–41.

APA	Demircan N, Engur C, Akın Telli T, Basoglu tuylu T, ARIKAN R, Yasar A, çelebi a, Alan O, ışık s, Özgüven S, Ercelep Ö, Dane F, Kaya H, Ones T, Yumuk P (2022). Association of Pre-treatment Sarcopenia with Side Effects and Prognosis in Non-small Cell Lung Cancer Patients Receiving Erlotinib. , 379 - 387. 10.5505/tjo.2022.3547
Chicago	Demircan Nazım Can,Engur Ceren Ozge,Akın Telli Tugba,Basoglu tuylu Tugba,ARIKAN RUKİYE,Yasar Alper,çelebi abdussamet,Alan Ozkan,ışık selver,Özgüven Salih,Ercelep Özlem,Dane Faysal,Kaya Handan,Ones Tunc,Yumuk Perran Fulden Association of Pre-treatment Sarcopenia with Side Effects and Prognosis in Non-small Cell Lung Cancer Patients Receiving Erlotinib. (2022): 379 - 387. 10.5505/tjo.2022.3547
MLA	Demircan Nazım Can,Engur Ceren Ozge,Akın Telli Tugba,Basoglu tuylu Tugba,ARIKAN RUKİYE,Yasar Alper,çelebi abdussamet,Alan Ozkan,ışık selver,Özgüven Salih,Ercelep Özlem,Dane Faysal,Kaya Handan,Ones Tunc,Yumuk Perran Fulden Association of Pre-treatment Sarcopenia with Side Effects and Prognosis in Non-small Cell Lung Cancer Patients Receiving Erlotinib. , 2022, ss.379 - 387. 10.5505/tjo.2022.3547
AMA	Demircan N,Engur C,Akın Telli T,Basoglu tuylu T,ARIKAN R,Yasar A,çelebi a,Alan O,ışık s,Özgüven S,Ercelep Ö,Dane F,Kaya H,Ones T,Yumuk P Association of Pre-treatment Sarcopenia with Side Effects and Prognosis in Non-small Cell Lung Cancer Patients Receiving Erlotinib. . 2022; 379 - 387. 10.5505/tjo.2022.3547
Vancouver	Demircan N,Engur C,Akın Telli T,Basoglu tuylu T,ARIKAN R,Yasar A,çelebi a,Alan O,ışık s,Özgüven S,Ercelep Ö,Dane F,Kaya H,Ones T,Yumuk P Association of Pre-treatment Sarcopenia with Side Effects and Prognosis in Non-small Cell Lung Cancer Patients Receiving Erlotinib. . 2022; 379 - 387. 10.5505/tjo.2022.3547
IEEE	Demircan N,Engur C,Akın Telli T,Basoglu tuylu T,ARIKAN R,Yasar A,çelebi a,Alan O,ışık s,Özgüven S,Ercelep Ö,Dane F,Kaya H,Ones T,Yumuk P "Association of Pre-treatment Sarcopenia with Side Effects and Prognosis in Non-small Cell Lung Cancer Patients Receiving Erlotinib." , ss.379 - 387, 2022. 10.5505/tjo.2022.3547
ISNAD	Demircan, Nazım Can vd. "Association of Pre-treatment Sarcopenia with Side Effects and Prognosis in Non-small Cell Lung Cancer Patients Receiving Erlotinib". (2022), 379-387. https://doi.org/10.5505/tjo.2022.3547

APA	Demircan N, Engur C, Akın Telli T, Basoglu tuylu T, ARIKAN R, Yasar A, çelebi a, Alan O, ışık s, Özgüven S, Ercelep Ö, Dane F, Kaya H, Ones T, Yumuk P (2022). Association of Pre-treatment Sarcopenia with Side Effects and Prognosis in Non-small Cell Lung Cancer Patients Receiving Erlotinib. Türk Onkoloji Dergisi, 37(4), 379 - 387. 10.5505/tjo.2022.3547
Chicago	Demircan Nazım Can,Engur Ceren Ozge,Akın Telli Tugba,Basoglu tuylu Tugba,ARIKAN RUKİYE,Yasar Alper,çelebi abdussamet,Alan Ozkan,ışık selver,Özgüven Salih,Ercelep Özlem,Dane Faysal,Kaya Handan,Ones Tunc,Yumuk Perran Fulden Association of Pre-treatment Sarcopenia with Side Effects and Prognosis in Non-small Cell Lung Cancer Patients Receiving Erlotinib. Türk Onkoloji Dergisi 37, no.4 (2022): 379 - 387. 10.5505/tjo.2022.3547
MLA	Demircan Nazım Can,Engur Ceren Ozge,Akın Telli Tugba,Basoglu tuylu Tugba,ARIKAN RUKİYE,Yasar Alper,çelebi abdussamet,Alan Ozkan,ışık selver,Özgüven Salih,Ercelep Özlem,Dane Faysal,Kaya Handan,Ones Tunc,Yumuk Perran Fulden Association of Pre-treatment Sarcopenia with Side Effects and Prognosis in Non-small Cell Lung Cancer Patients Receiving Erlotinib. Türk Onkoloji Dergisi, vol.37, no.4, 2022, ss.379 - 387. 10.5505/tjo.2022.3547
AMA	Demircan N,Engur C,Akın Telli T,Basoglu tuylu T,ARIKAN R,Yasar A,çelebi a,Alan O,ışık s,Özgüven S,Ercelep Ö,Dane F,Kaya H,Ones T,Yumuk P Association of Pre-treatment Sarcopenia with Side Effects and Prognosis in Non-small Cell Lung Cancer Patients Receiving Erlotinib. Türk Onkoloji Dergisi. 2022; 37(4): 379 - 387. 10.5505/tjo.2022.3547
Vancouver	Demircan N,Engur C,Akın Telli T,Basoglu tuylu T,ARIKAN R,Yasar A,çelebi a,Alan O,ışık s,Özgüven S,Ercelep Ö,Dane F,Kaya H,Ones T,Yumuk P Association of Pre-treatment Sarcopenia with Side Effects and Prognosis in Non-small Cell Lung Cancer Patients Receiving Erlotinib. Türk Onkoloji Dergisi. 2022; 37(4): 379 - 387. 10.5505/tjo.2022.3547
IEEE	Demircan N,Engur C,Akın Telli T,Basoglu tuylu T,ARIKAN R,Yasar A,çelebi a,Alan O,ışık s,Özgüven S,Ercelep Ö,Dane F,Kaya H,Ones T,Yumuk P "Association of Pre-treatment Sarcopenia with Side Effects and Prognosis in Non-small Cell Lung Cancer Patients Receiving Erlotinib." Türk Onkoloji Dergisi, 37, ss.379 - 387, 2022. 10.5505/tjo.2022.3547
ISNAD	Demircan, Nazım Can vd. "Association of Pre-treatment Sarcopenia with Side Effects and Prognosis in Non-small Cell Lung Cancer Patients Receiving Erlotinib". Türk Onkoloji Dergisi 37/4 (2022), 379-387. https://doi.org/10.5505/tjo.2022.3547