The impact of SARS-CoV-2 infection on the survival in NSCLC patients undergoing immunotherapy

Abstract

Purpose: The impact of immune checkpoint inhibitor (ICI) utilisation on prognosis and the prognostic value of inflammatory markers (neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), systemic immune inflammation score (SII), prognostic nutrition index (PNI)) in patients with advanced non-small cell lung cancer (NSCLC) were evaluated in the context of the ongoing pandemic. The cut-off values of the prognostic markers were obtained from clinical studies in the literature. Materials and methods: A non-probability sequential sampling technique ensured the study included 104 patients who had received ICI at any stage. Laboratory tests taken at the outset of ICI treatment were recorded, and NLR, PLR, PNI and SII were calculated and 2-year median overall survival (mOS) was then evaluated. Results: The median age of the cohort was 63.99 years, with 98% of patients being male. Infection with SARS-CoV-2 virus was documented in 29 patients (27.9%). The survival results were similar in both groups when the cut-off values were applied for inflamatuar markers. The two-year mOS was 22 months (44.1%). The two-year survival rate of patients who developed a SARS-CoV-2 infection following the administration of an ICI at any stage of treatment was inferior to that of ICI recipients who did not develop the infection (14.3 months vs. 53.6 months; p=0.001). In contrast with previous studies, 57.1% of patients with a PD-L1 level of 0 survived for two years, while only 10% with levels of 1-49 did so (p=0.010). Conclusion: This study revealed a significantly lower two-year survival rate in patients with a positive diagnosis for SARS-CoV-2 during ICI use compared to those without a positive diagnosis (14.3 months; 53.6 months; p=0.001). In the course of our research, we were unsuccessful in identifying a prognostic marker that could be useful in predicting survival in NSCLC patients using ICI in the context of the pandemic. This investigation yielded findings that differed from the conclusions of previous studies. It demonstrated that, contrary to the prevailing view, the two-year survival rate was higher in patients exhibiting PD-L1 '0' than in those with PD-L1:1-49 (57.1%; 10%, p=0.010).

Keywords

• NSCLC
• COVID-19
• immunotherapy

İmmünoterapi uygulanan NSCLC hastalarında SARS-CoV-2 enfeksiyonunun sağkalım üzerine etkisi

Abstract

Amaç: İleri evre küçük hücreli dışı akciğer kanserli (NSCLC) hastalarda immün kontrol noktası inhibitörü (ICI) kullanımının prognoz üzerindeki etkisi ve inflamatuar belirteçlerin (nötrofil-lenfosit oranı (NLR), trombosit-lenfosit oranı (PLR), sistemik immün inflamasyon skoru (SII), prognostik beslenme indeksi (PNI)) prognostik değeri devam eden pandemi bağlamında değerlendirildi. Gereç ve yöntem: Olasılıksız sıralı örnekleme tekniği ile belirlenen tedavinin herhangi bir basamağında ICI almış 104 hastanın çalışmaya dahil edildi. ICI tedavisinin başlangıcında alınan laboratuvar testleri kaydedilerek; NLR, PLR, PNI ve SII hesaplandı. Ardından 2 yıllık medyan genel sağkalım (mOS) değerlendirildi. Prognostik belirteçlerin cut-off değerleri literatürde yer alan klinik çalışmalardan elde edildi. Bulgular: Ortalama tanı yaşı 63,99 yıl olup hastaların %98'i erkekti. SARS-CoV-2 virüsü ile enfekte olan 29 hasta (%27,9) vardı. Enflamatuar belirteçler için kesme değerler uygulandığında sağkalım sonuçları her iki grupta da benzerdi. İki yıllık mOS 22 aydı (%44,1). Tedavinin herhangi bir aşamasında ICI uygulanmasını takiben SARS-CoV-2 enfeksiyonu gelişen hastaların iki yıllık sağkalım oranı, enfeksiyon gelişmeyen ICI alıcılarınınkinden daha düşüktü (14,3 ay; 53,6 ay; p=0,001). Önceki çalışmaların aksine, PD-L1 düzeyi 0 olan hastaların %57,1'i iki yıl boyunca hayatta kalırken, 1-49 düzeyine sahip hastaların yalnızca %10'u hayatta kalmıştır (p=0,010). Sonuç: Bu çalışma, ICI kullanımı sırasında SARS-CoV-2 için pozitif tanı alan hastalarda, pozitif tanı almayanlara kıyasla iki yıllık sağkalım oranının anlamlı derecede düşük olduğunu ortaya koymuştur (14,3 ay; 53,6 ay; p=0,001). Araştırmamızda, pandemi döneminde ICI kullanan NSCLC hastalarında sağkalımı tahmin etmede yararlı olabilecek bir prognostik belirteç tanımlayamadık. Bu araştırma, önceki çalışmaların sonuçlarından farklı olarak, iki yıllık sağkalım oranının PD-L1:'0' olan hastalarda PD-L1:1-49 gösterenlere göre daha yüksek olduğunu göstermiştir (%57,1; %10, p=0,010).

Keywords

• NSCLC
• COVID-19
• immünoterapi

References

1. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74:229-263. doi:10.3322/caac.21834
2. Zhao XH, Shen WB, Wang D, Wang HS, Song CY, Deng WZ. The prognosis value of CONUT and SIS score for recurrent or metastatic esophageal squamous cell carcinoma patients treated with second-line immunotherapy. Front Oncol. 2023;13:1167625. doi:10.3389/fonc.2023.1167625
3. Zhao ZW, Chen Q, Zhang XT, Luo YK. The CONUT score predicts the length of hospital stay and the risk of long COVID. Nutr Hosp. 2024;41:138-144. doi:10.20960/nh.04656
4. Zhu N, Zhang D, Wang W, et al. China Novel Coronavirus Investigating and Research Team. A novel Coronavirus from patients with pneumonia in China, N Engl J Med. 2020;382:727-733. doi:10.1056/NEJMoa2001017
5. Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med. 2012;367:1814-1820. doi:10.1056/NEJMoa1211721
6. Zhong NS, Zheng BJ, Li YM, et al. Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People's Republic of China. Lancet. 2003;362:1353-1358. doi:10.1016/s0140-6736(03)14630-2
7. Lauer SA, Grantz KH, Bi Q, et al. The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and application. Ann Intern Med. 2020;172:577-582. doi:10.7326/M20-0504
8. Garg S, Kim L, Whitaker M, et al. Hospitalization Rates and Characteristics of Patients Hospitalized with Laboratory-Confirmed Coronavirus Disease 2019 - COVID-NET, 14 States. MMWR Morb Mortal Wkly Rep. 2020;69:458-464. doi:10.15585/mmwr.mm6915e3

9. Zhang D, Zhuang D, Li T, et al. An analysis of neutrophil-to-lymphocyte ratios and monocyte-to-lymphocyte ratios with six-month prognosis after cerebral contusions. Front Immunol. 2024;15:1336862. doi:10.3389/fimmu.2024.1336862
10. Wang L, Li X, Liu M, Zhou H, Shao J. Association between monocyte-to-lymphocyte ratio and prostate cancer in the U.S. population: a population-based study. Front Cell Dev Biol. 2024;12:1372731. doi:10.3389/fcell.2024.137273
11. Menyhart O, Fekete JT, Győrffy B. Inflammation and Colorectal Cancer: A Meta-Analysis of the Prognostic Significance of the Systemic Immune-Inflammation Index (SII) and the Systemic Inflammation Response Index (SIRI). Int J Mol Sci. 2024;25(15):8441. doi:10.3390/ijms25158441
12. Erciyestepe M, Selvi O, Dinç Sonuşen Ş, et al. Prognostic Value of Inflammation and Nutrition-Based Scores in Non-Small-Cell-Lung-Cancer. Med Princ Pract. 2024;33(2):122-132. doi:10.1159/000535781
13. Diakos CI, Charles KA, McMillan DC, Clarke SJ. Cancer related inflammation and treatment effectiveness. Lancet Oncol. 2014;15:493-503. doi:10.1016/S1470-2045(14)70263-3
14. Fosbol EL, Butt JH, Ostergaard L, et al. Association of angiotensin-converting enzyme ınhibitor or angiotensin receptor blocker use with COVID-19 diagnosis and mortality. JAMA. 2020;324:168-177. doi:10.1001/jama.2020.11301
15. Cai C, Gao Y, Adamo S, et al. SARS CoV-2 vaccination enhances the effector qualities of spike specific T cells induced by COVID-19. Sci Immunol. 2023;8:eadh0687. doi:10.1126/sciimmunol.adh0687
16. Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020;8:420-422. doi:10.1016/S2213-2600(20)30076-X
17. Thachil J, Tang N, Gando S, et al. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost. 2020;18:1023-1026. doi:10.1111/jth.14810
18. Jung YJ, Ahn J, Park S, et al. Machine learning prediction of the case-fatality of COVID-19 and risk factors for adverse outcomes in patients with non-small cell lung cancer. Transl Cancer Res. 2024;13:2587-2595. doi:10.21037/tcr-23-2188
19. Orelaru F, Edwards M, Raleigh R, et al. Short term outcomes of COVID-19 pandemic on non small cell lung cancer screening and management. Surg J (N Y). 2023;9:156-161. doi:10.1055/s-0043-1777856
20. Yang Y, Niu L, Zhu Y, et al. Optimum timing of lung resection surgery following SARS-CoV-2 infection for non small cell lung cancer. Cancer Med. 2024;13:6891. doi:10.1002/cam4.6891
21. Ricciuti B, Dahlberg SE, Adeni A, Sholl LM, Nishino M, Awad MM. Immune Checkpoint Inhibitor Outcomes for Patients With Non-Small-Cell Lung Cancer Receiving Baseline Corticosteroids for Palliative Versus Nonpalliative Indications. J Clin Oncol. 2019;37:1927-1934. doi:10.1200/JCO.19.00189