Impact of obstructive sleep apnea risk on prognosis and treatment responses of lung cancer

Yıl 2024, , 97 - 104, 30.04.2024

Sezgi Şahin Duyar , Pınar Akın Kabalak , Selma Fırat , Ülkü Yılmaz , Derya Kızılgöz , Suna Kavurgacı

https://doi.org/10.47582/jompac.1442684

Öz

Aims: Obstructive sleep apnea (OSA) may affect oncogenic processes in a specific way for each tumor type. This study was conducted to reveal the relationship between OSA risk and prognosis and treatment responses in patients with lung cancer.
Methods: This prospective study included stage III and IV lung cancer patients aged between 18 and 75 years. Patients with poor performance status, cranial metastasis, congestive heart failure, surgery history, and positive airway pressure device use were excluded. STOP-BANG questionnaire was used to assess the OSA risk. The primary end-point was the differences in the survival and treatment responses of patients at intermediate/high risk of OSA compared with those at low OSA risk. Data from the patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) were analyzed separately.
Results: Ninety-eight patients (34 SCLC and 64 NSCLC), mostly male (85.7%), with a mean age of 59.3±8 were included in the analysis. Overall survival was similar in the groups. However, in the SCLC group, those at low OSA risk had a shorter progression-free survival (PFS) than those at intermediate/high risk (105±31.8 days, vs 272±16.2 days, p=0.001). Cox regression analysis showed that low OSA risk was an independent risk factor for PFS in only the SCLC group (HR:4.9 CI:1.6-14.7, p=0.005).
Conclusion: IOur results showed that low OSA risk was an independent poor prognostic factor for PFS in SCLC regardless of the tumor stage.

Anahtar Kelimeler

Lung cancer, obstructive sleep apnea, overall survival, progression-free survival, STOP-BANG questionnaire

Obstrüktif uyku apnesi riskinin akciğer kanserinin prognozu ve tedavi yanıtlarına etkisi

Öz

Amaç: Obstrüktif uyku apnesi (OSA), her tümör tipi için onkojenik süreçleri spesifik bir şekilde etkileyebilir. Bu çalışma akciğer kanserli hastalarda OSA riski ile prognoz ve tedavi yanıtları arasındaki ilişkiyi ortaya koymak amacıyla yapılmıştır.
Yöntemler: Bu prospektif çalışmaya 18-75 yaşları arasındaki evre III ve IV akciğer kanseri hastaları dahil edildi. Performans durumu kötü olan, kranial metastazı olan, konjestif kalp yetmezliği olan, ameliyat öyküsü olan ve pozitif hava yolu basıncı cihazı kullanan hastalar çalışma dışı bırakıldı. OSA riskini değerlendirmek için STOP-BANG anketi kullanıldı. Birincil sonlanım noktası olarak, düşük OSA riski olan hastalar orta/yüksek OSA riski taşıyanlarla sağkalım ve tedavi yanıtlarındaki farklılıklar açısından karşılaştırıldı. Küçük hücreli dışı akciğer kanseri (KHDAK) ve küçük hücreli akciğer kanseri (KHAK) hastalarına ait veriler ayrı ayrı analiz edildi.
Bulgular: Analize yaş ortalaması 59,3±8 olan, çoğu erkek (%85,7) olmak üzere 98 hasta (34 KHAK ve 64 KHDAK) dahil edildi. Genel sağkalım gruplarda benzerdi. Bununla birlikte, KHAK grubunda düşük OSA riski taşıyanların progresyonsuz sağkalım (PFS) süresi orta/yüksek riskli olanlara göre daha kısaydı (105±31,8 gün, vs 272±16,2 gün, p=0,001). Cox regresyon analizi, düşük OSA riskinin yalnızca KHAK grubunda PFS için bağımsız bir risk faktörü olduğunu gösterdi (HR:4,9 CI:1,6-14,7, p=0,005).
Sonuç: Sonuçlarımız, düşük OSA riskinin, tümör evresinden bağımsız olarak KHAK'de PFS için kötü prognostik faktör olduğunu göstermektedir.

Anahtar Kelimeler

Akciğer kanseri, obstrüktif uyku apnesi, genel sağkalım, progresyonsuz sağkalım, STOP-BANG anketi

Kaynakça

• 1. Almendros I, Gozal D. Intermittent hypoxia and cancer: undesirable bed partners? Respir Physiol Neurobiol. 2018;256:79-86. doi: 10.1016/j.resp.2017.08.008
• 2. Gozal D, Almendros I, Phipps AI, Campos-Rodriguez F, Martínez-García MA, Farré R. Sleep apnoea adverse effects on cancer: true, false, or too many confounders? Int J Mol Sci. 2020;21(22):8779. doi: 10.3390/ijms21228779
• 3. Almendros I, Wang Y, Becker L, et al. Intermittent hypoxia-induced changes in tumor-associated macrophages and tumor malignancy in a mouse model of sleep apnea. Am J Respir Crit Care Med. 2014;189(5):593-601. doi: 10.1164/rccm.201310-1830OC
• 4. Martinez CA. Kerr B, Jin C, Cistulli PA, Cook KM. Obstructive sleep apnea activates hif-1 in a hypoxia dose-dependent manner in hct116 colorectal carcinoma cells. Int J Mol Sci. 2019;20(2):445.
• 5. Verduzco D, Lloyd M, Xu L, et al. Intermittent hypoxia selects for genotypes and phenotypes that increase survival, invasion, and therapy resistance. PLoS One. 2015;10(3):e0120958. doi: 10.1371/journal.pone.0120958
• 6. Hakim F, Wang Y, Zhang SX, et al. Fragmented sleep accelerates tumor growth and progression through recruitment of tumor-associated macrophages and TLR4 signaling. Cancer Res. 2014;74(5):1329-1337. doi: 10.1158/0008-5472.CAN-13-3014
• 7. Cortés-Hernández LE, Eslami-S Z, Dujon AM, et al. Domalignant cells sleep at night? Genome Biol. 2020;21(1):276.
• 8. Kendzerska T, Leung RS, Hawker G, Tomlinson G, Gershon AS. Obstructive sleep apnea and the prevalence and incidence of cancer. CMAJ. 2014;186(13):985-992.
• 9. Zhang XB, Peng LH, Lyu Z, Jiang XT, Du YP. Obstructive sleep apnoea and the incidence and mortality of cancer: a metaanalysis. Eur J Cancer Care. 2017;26(2):e12427.
• 10. Campos-Rodriguez F, Martinez-Garcia MA, Martinez M, et al. Association between obstructive sleep apnea and cancer incidence in a large multicenter Spanish cohort. Am J Respir Crit Care Med. 2013;187(1):99-105.
• 11. Nieto FJ, Peppard PE, Young T, Finn L, Hla KM, Farre R. Sleep-disordered breathing and cancer mortality: results from the Wisconsin Sleep Cohort Study. Am J Respir Crit Care Med. 2012;186(2):190-194.
• 12. Gozal D, Ham SA, Mokhlesi B. Sleep apnea and cancer: analysis of a nationwide population sample. Sleep. 2016;39(8):1493-1500.
• 13. Lifeng Li. Target of obstructive sleep apnea syndrome merge lung cancer: based on big data platform. Oncotarget. 2017;8(13):21954-21973.
• 14. Rami-Porta R, Asamura H, Travis WD, Rusch VW. Lung cancer-major changes in the American Joint Committee on Cancer eighth edition staging manual. CA Cancer J Clin. 2017;67(2):138-155. doi: 10.3322/caac.21390
• 15. Kalemkerian GP. Staging and imaging of small cell lung cancer. Cancer Imaging. 2011;11(1):253-258. doi: 10.1102/1470-7330.2011.0036
• 16. Topuz MF, Ture N, Akdag G, Arik O, Gulhan PY. The importance of systemic immune-inflammation index in obstructive sleep apnea syndrome. Eur Arch Otorhinolaryngol. 2022;279(10):5033-5038. doi: 10.1007/s00405-021-07227-0
• 17. Chung F, Yang Y, Brown R, Liao P. Alternative scoring models of STOP-bang questionnaire improve specificity to detect undiagnosed obstructive sleep apnea. J Clin Sleep Med. 2014;10(9):951-958. doi: 10.5664/jcsm.4022
• 18. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228-247. doi: 10.1016/j.ejca.2008.10.026
• 19. Carreras A, Kayali F, Zhang J, Hirotsu C, Wang Y, Gozal D. Metabolic effects of intermittent hypoxia in mice: steady versus high-frequency applied hypoxia daily during the rest period. Am J Physiol Regul Integr Comp Physiol. 2012;303(7):R700-R709. doi: 10.1152/ajpregu.00258.2012
• 20. Vilaseca A, Vertosick EA, Nguyen DP, et al. MP50-18 obstructive sleep apnea and high Fuhrman grade in patients with clear cell renal cell carcinoma treated with nephrectomy. J Urol. 2015;193(4S), e618-e618.
• 21. Chen A, Sceneay J, Gödde N, Kinwel T, et al. Intermittent hypoxia induces a metastatic phenotype in breast cancer. Oncogene. 2018;37(31):4214-4225.
• 22. Yoon DW, Kim Y, Hwang S, et al. Intermittent hypoxia promotes carcinogenesis in azoxymethane and dextran sodium sulfate-induced colon cancer model. Mol Carcinog. 2019;58(5):654-665.
• 23. Ali M, Kowkuntla S, Delloro DJ, et al. Chronic intermittent hypoxia enhances disease progression in myeloma-resistant mice. Am J Physiol-Regul Integr Comp Physiol. 2019;316:R678-R686.
• 24. Martínez-García MÁ, Campos-Rodriguez F, Barbé F. Cancer and OSA: current evidence from human studies. Chest. 2016;150(2):451-463. doi: 10.1016/j.chest.2016.04.029
• 25. Christensen AS, Clark A, Salo P, et al. Symptoms of sleep-disordered breathing and risk of cancer: a prospective cohort study. Sleep. 2013;36(10):1429-1435.
• 26. Martínez-García MA, Campos-Rodriguez F, Durán-Cantolla J, et al. Obstructive sleep apnea is associated with cancer mortality in younger patients. Sleep Med. 2014;15(7):742-748.
• 27. Marshall NS, Wong KK, Cullen SRJ, Knuiman MW, Grunstein RR. Sleep apnea and 20-year follow-up for all-cause mortality, stroke, and cancer incidence and mortality in the Busselton Health Cohort Study. J Clin Sleep Med. 2014;10(4):355-362.
• 28. Martínez-García MÁ, Martorell-Calatayud A, Nagore E, et al. Association between sleep disordered breathing and aggressiveness markers of malignant cutaneous melanoma. Eur Respir J. 2014;43(6):1661-1668.
• 29. Friedman M, Landsberg R, Pryor S, Syed Z, Ibrahim H, Caldarelli DD. The occurrence of sleep-disordered breathing among patients with head and neck cancer. Laryngoscope. 2011;111(6):1917-1919.
• 30. Payne RJ, Hier MP, Kost KM, et al. High prevalence of obstructive sleep apnea among patients with head and neck cancer. J Otolaryngol. 2005;34(5):304-311.
• 31. Cheong AJY, Tan BKJ, Teo YH, et al. Obstructive sleep apnea and lung cancer: a systematic review and meta-analysis. Ann Am Thorac Soc. 2022;19(3):469-475. doi: 10.1513/AnnalsATS.202108- 960OC
• 32. Hao S, Zhu X, Liu Z, et al. Chronic intermittent hypoxia promoted lung cancer stem cell-like properties via enhancing Bach1 expression. Respir Res. 2021;22(1):58. doi: 10.1186/s12931-021-01655-6
• 33. Gu X, Zhang J, Shi Y, et al. ESM1/HIF-1α pathway modulates chronic intermittent hypoxia-induced non-small-cell lung cancer proliferation, stemness and epithelial-mesenchymal transition. Oncol Rep. 2021;45(3):1226-1234. doi: 10.3892/or.2020.7913
• 34. Huang HY, Lin SW, Chuang LP, et al. Severe OSA associated with higher risk of mortality in stage III and IV lung cancer. J Clin Sleep Med. 2020;16(7):1091-1098. doi: 10.5664/jcsm.8432
• 35. Chen MX, Chen LD, Zeng AM, et al. Obstructive sleep apnea and the risk of mortality in patients with lung cancer: a meta-analysis. Sleep Breath. 2022;26(2):559-566. doi: 10.1007/s11325-021-02416-x
• 36. Zhou W, Dosey TL, Biechele T, Moon RT, Horwitz MS, Ruohola-Baker H. Assessment of hypoxia inducible factor levels in cancer cell lines upon hypoxic induction using a novel reporter construct. PLoS One. 2011;6(11):e27460. doi: 10.1371/journal.pone.0027460.
• 37. Cosse JP, Sermeus A, Vannuvel K, Ninane N, Raes M, Michiels C. Differential effects of hypoxia on etoposide-induced apoptosis according to the cancer cell lines. Mol Cancer. 2007;6(1):61. doi: 10.1186/1476-4598-6-61.
• 38. Kapur VK, Auckley DH, Chowdhuri S, et al. Clinical Practice Guideline for Diagnostic Testing for Adult Obstructive Sleep Apnea: An American Academy of Sleep Medicine Clinical Practice Guideline. J Clin Sleep Med. 2017;13(3):479-504 doi: 10.5664/jcsm.6506
• 39. Marhuenda E, Campillo N, Gabasa M, et al. Effects of sustained and intermittent hypoxia on human lung cancer cells. Am J Respir Cell Mol Biol. 2019;61(4):540-544. doi:10.1165/rcmb.2018-0412LE