Prognostic Impact of Infectious Agents After Definitive Treatment in Non-Small Cell Lung Cancer
Abstract
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patient Selection
2.2. Treatment and Follow-Up
2.3. Data Collection
2.4. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Siegel, R.L.; Kratzer, T.B.; Giaquinto, A.N.; Sung, H.; Jemal, A. Cancer Statistics, 2025. CA Cancer J. Clin. 2025, 75, 10–45. [Google Scholar] [CrossRef]
- Obradović, J.; Niševic-Lazović, J.; Sekeruš, V.; Milašin, J.; Perin, B.; Jurisic, V. Investigating the Frequencies of EGFR Mutations and EGFR Single Nucleotide Polymorphisms Genotypes and Their Predictive Role in NSCLC Patients in Republic of Serbia. Mol. Biol. Rep. 2025, 52, 350. [Google Scholar] [CrossRef]
- Jurišić, V.; Obradovic, J.; Pavlović, S.; Djordjevic, N. Epidermal Growth Factor Receptor Gene in Non-Small-Cell Lung Cancer: The Importance of Promoter Polymorphism Investigation. Anal. Cell. Pathol. 2018, 2018, 6192187. [Google Scholar] [CrossRef]
- Sarihan, S.; Ercan, I.; Saran, A.; Çetintas, S.K.; Akalin, H.; Engin, K. Evaluation of Infections in Non-Small Cell Lung Cancer Patients Treated with Radiotherapy. Cancer Detect. Prev. 2005, 29, 181–188. [Google Scholar] [CrossRef]
- Vento, S.; Cainelli, F.; Temesgen, Z. Lung Infections after Cancer Chemotherapy. Lancet Oncol. 2008, 9, 982–992. [Google Scholar] [CrossRef] [PubMed]
- Perlin, E.; Bang, K.M.; Shah, A.; Hursey, P.D.; Whittingham, W.L.; Hashmi, K.; Campbell, L.; Kassim, O.O. The Impact of Pulmonary Infections on the Survival of Lung Cancer Patients. Cancer 1990, 66, 593–596. [Google Scholar] [CrossRef]
- Remiszewski, P.; Słodkowska, J.; Wiatr, E.; Zych, J.; Radomski, P.; Rowińska-Zakrzewska, E. Fatal Infection in Patients Treated for Small Cell Lung Cancer in the Institute of Tuberculosis and Chest Diseases in the Years 1980–1994. Lung Cancer 2001, 31, 101–110. [Google Scholar] [CrossRef]
- Liu, C.; Cui, H.; Gu, D.; Zhang, M.; Fang, Y.; Chen, S.; Tang, M.; Zhang, B.; Chen, H. Genetic Polymorphisms and Lung Cancer Risk: Evidence from Meta-Analyses and Genome-Wide Association Studies. Lung Cancer 2017, 113, 18–29. [Google Scholar] [CrossRef]
- Zaorsky, N.G.; Churilla, T.M.; Egleston, B.L.; Fisher, S.G.; Ridge, J.A.; Horwitz, E.M.; Meyer, J.E. Causes of Death among Cancer Patients. Ann. Oncol. 2017, 28, 400–407. [Google Scholar] [CrossRef]
- Radouani, F.; El Yazouli, L.; Elyazghi, Z.; Hejaji, H.; Alami, A.A.; Elmdaghri, N. Chlamydia Pneumoniae Sero-Prevalence in Moroccan Patients with Cardiovascular Diseases. Infect. Dis. Health 2019, 24, 67–74. [Google Scholar] [CrossRef]
- Aupérin, A.; Le Péchoux, C.; Rolland, E.; Curran, W.J.; Furuse, K.; Fournel, P.; Belderbos, J.; Clamon, G.; Ulutin, H.C.; Paulus, R.; et al. Meta-Analysis of Concomitant Versus Sequential Radiochemotherapy in Locally Advanced Non–Small-Cell Lung Cancer. J. Clin. Oncol. 2010, 28, 2181–2190. [Google Scholar] [CrossRef]
- Dillman, R.O.; Herndon, J.; Seagren, S.L.; Eaton, W.L.; Green, M.R. Improved Survival in Stage III Non-Small-Cell Lung Cancer: Seven-Year Follow-up of Cancer and Leukemia Group B (CALGB) 8433 Trial. JNCI J. Natl. Cancer Inst. 1996, 88, 1210–1215. [Google Scholar] [CrossRef]
- Obradovic, J.; Todosijevic, J.; Jurisic, V. Side Effects of Tyrosine Kinase Inhibitors Therapy in Patients with Non-Small Cell Lung Cancer and Associations with EGFR Polymorphisms: A Systematic Review and Meta-Analysis. Oncol. Lett. 2023, 25, 62. [Google Scholar] [CrossRef] [PubMed]
- Charlson, M.E.; Pompei, P.; Ales, K.L.; MacKenzie, C.R. A New Method of Classifying Prognostic Comorbidity in Longitudinal Studies: Development and Validation. J. Chronic Dis. 1987, 40, 373–383. [Google Scholar] [CrossRef]
- Horan, T.C.; Andrus, M.; Dudeck, M.A. CDC/NHSN Surveillance Definition of Health Care—Associated Infection and Criteria for Specific Types of Infections in the Acute Care Setting. Am. J. Infect. Control 2008, 36, 309–332. [Google Scholar] [CrossRef]
- Unal, I. Defining an Optimal Cut-Point Value in ROC Analysis: An Alternative Approach. Comput. Math. Methods Med. 2017, 2017, 3762651. [Google Scholar] [CrossRef] [PubMed]
- Yang, Z.; Qin, X.; Lu, Y.; Yao, L.; Liu, A.; Yu, Q.; Jiang, W.; Liang, J.; Li, Y.; Zhou, S.; et al. Pathogen Spectrum and Clinical Characteristics of Lung Cancer Patients: A 10-year Retrospective Study. Int. J. Cancer 2025, 156, 1470–1479. [Google Scholar] [CrossRef]
- Patel, A.J.; Nightingale, P.; Naidu, B.; Drayson, M.T.; Middleton, G.W.; Richter, A. Characterising the Impact of Pneumonia on Outcome in Non-Small Cell Lung Cancer: Identifying Preventative Strategies. J. Thorac. Dis. 2020, 12, 2236–2246. [Google Scholar] [CrossRef] [PubMed]
- Qin, W.; You, T.; Guo, T.; Tian, R.; Cui, X.; Wang, P. The Inter-Relationships Among the Risk Factors for Pulmonary Infection and the Diagnostic Utility of Inflammatory Markers in Patients with Non-Small Cell Lung Cancer. Infect. Drug Resist. 2025, 18, 1111–1123. [Google Scholar] [CrossRef]
- Shan, H.; Wang, J.; Zhang, Q.; Ming, Z.; Zhang, Y.; He, P.; Fang, P.; Zhang, M.; Li, W.; Shi, H.; et al. Pathogen Surveillance and Risk Factors for Pulmonary Infection in Patients with Lung Cancer: A Retrospective Single-Center Study. Open Med. 2025, 20, 20251180. [Google Scholar] [CrossRef]
- Petrovic, S.; Beovic, B.; Tomic, V.; Bitenc, M.; Malovrh, M.M.; Dimitric, V.; Luznik, D.; Miklavcic, M.; Bozic, T.; Gabrovec, T.; et al. Bronchial Bacterial Colonization and the Susceptibility of Isolated Bacteria in Patients with Lung Malignancy. Radiol. Oncol. 2025, 59, 147–152. [Google Scholar] [CrossRef] [PubMed]
- Qiao, D.; Wang, Z.; Lu, Y.; Wen, X.; Li, H.; Zhao, H. A Retrospective Study of Risk and Prognostic Factors in Relation to Lower Respiratory Tract Infection in Elderly Lung Cancer Patients. Am. J. Cancer Res. 2015, 5, 423–432. [Google Scholar]
- Abd-Elmonsef, M.M.E.; Elsharawy, D.; Abd-Elsalam, A.S. Mechanical Ventilator as a Major Cause of Infection and Drug Resistance in Intensive Care Unit. Environ. Sci. Pollut. Res. 2018, 25, 30787–30792. [Google Scholar] [CrossRef]
- de Kermenguy, F.; Morel, D.; El-Aichi, M.; Barbolosi, D.; Deutsch, E.; Robert, C. Radiation-Induced Lymphopenia: From Mathematical Modeling Towards Mechanistic Learning. Int. J. Radiat. Oncol. Biol. Phys. 2025; in press. [Google Scholar] [CrossRef]
- Pajic, J.; Milic, M.; Jurisic, V.; Vinnikov, V. Editorial: Research on Low Dose Ionizing Radiation Health Effects. Front. Public. Health 2025, 13, 1566179. [Google Scholar] [CrossRef] [PubMed]
- Valvani, A.; Martin, A.; Devarajan, A.; Chandy, D. Postobstructive Pneumonia in Lung Cancer. Ann. Transl. Med. 2019, 7, 357. [Google Scholar] [CrossRef]
- Jurisic, V.; Colovic, N.; Konjevic, G.; Minic, I.; Colovic, M. An Aggressive Extramedullary Cutaneous Plasmacytoma Associated with Extreme Alterations in the Innate Immune System. Onkologie 2010, 33, 113–115. [Google Scholar] [CrossRef]
- Bertaglia, V.; Morelli, A.M.; Solinas, C.; Aiello, M.M.; Manunta, S.; Denaro, N.; Tampellini, M.; Scartozzi, M.; Novello, S. Infections in Lung Cancer Patients Undergoing Immunotherapy and Targeted Therapy: An Overview on the Current Scenario. Crit. Rev. Oncol. Hematol. 2023, 184, 103954. [Google Scholar] [CrossRef]
- Belluomini, L.; Caldart, A.; Avancini, A.; Dodi, A.; Trestini, I.; Kadrija, D.; Sposito, M.; Tregnago, D.; Casali, M.; Riva, S.T.; et al. Infections and Immunotherapy in Lung Cancer: A Bad Relationship? Int. J. Mol. Sci. 2020, 22, 42. [Google Scholar] [CrossRef]
- Wang, X.; Wu, Y.; Hu, W.; Zhang, J. Incidence and Risk Factors of Serious Infections Occurred in Patients with Lung Cancer Following Immune Checkpoint Blockade Therapy. BMC Cancer 2025, 25, 307. [Google Scholar] [CrossRef] [PubMed]
Characteristic | n (%) | |
---|---|---|
Gender | Male | 187 (87.4%) |
Female | 27 (12.6%) | |
Age | <65 years | 103 (48.1%) |
≥65 years | 111 (51.9%) | |
Education Level | Primary education | 33 (15.4%) |
Lower secondary education | 68 (31.8%) | |
Upper secondary education | 92 (43%) | |
Tertiary education | 21 (9.8%) | |
Place of Residence | Urban | 157 (73.4%) |
Rural | 57 (26.6%) | |
Income Level | Low | 38 (17.7%) |
Middle | 151 (70.6%) | |
High | 25 (11.7%) | |
BMI | <18.5 kg/m2 | 11 (5.1%) |
18.5–24.9 kg/m2 | 102 (47.7%) | |
25.0–29.9 kg/m2 | 62 (29%) | |
≥30 kg/m2 | 39 (18.2%) | |
Pulmonary Comorbidities | None | 162 (75.7%) |
COPD | 40 (18.7%) | |
Asthma | 9 (4.2%) | |
Other | 3 (1.4%) | |
Diabetes Mellitus | Yes | 38 (17.8%) |
No | 176 (82.2%) | |
Charlson Comorbidity Index | 1–2 (mild) | 11 (5.1%) |
3–5 (moderate) | 152 (71.1%) | |
≥6 (severe) | 51 (23.8%) | |
Histopathology | Squamous cell carcinoma | 124 (57.9%) |
Adenocarcinoma | 61 (28.5%) | |
Other | 29 (13.6%) | |
T Stage | T1 | 15 (7%) |
T2 | 58 (27.1%) | |
T3 | 48 (22.4%) | |
T4 | 93 (43.5%) | |
N Stage | N0 | 42 (19.6%) |
N1 | 12 (5.6%) | |
N2 | 140 (65.4%) | |
N3 | 20 (9.4%) | |
TNM Stage | Stage I | 5 (2.3%) |
Stage II | 15 (7%) | |
Stage III | 183 (85.6%) | |
Stage IV | 11 (5.1%) | |
Treatment Modality | CRT | 151 (70.6%) |
IC + CRT | 59 (27.6%) | |
RT alone | 4 (1.8%) | |
RT Dose | 60 Gy | 169 (79%) |
66 Gy | 41 (19.2%) | |
Other | 4 (1.8%) |
Characteristic | n (%) * | |
---|---|---|
Culture Status | Positive | 45 (21.1%) |
Negative | 66 (30.8%) | |
Not taken | 103 (48.1%) | |
Culture Site | Sputum | 29 (13.5%) |
Tracheal aspirate | 6 (2.8%) | |
Blood culture | 10 (4.6%) | |
Growth | Monomicrobial growth | 38 (17.7%) |
Dual-organism growth | 7 (3.3%) | |
HAI | Yes | 26 (12.2%) |
No | 19 (8.9%) |
P. aeruginosa (n = 8) | A. baumannii (n = 6) | E. coli (n = 3) | K. pneumoniae (n = 1) | |||||
---|---|---|---|---|---|---|---|---|
AK | - | - | 6 | (100) | - | - | - | - |
AMC | * | * | * | 1 | (100) | |||
Ceftazidime | 8 | (100) | * | - | - | - | - | |
Ciprofloxacin | * | * | 3 | (100) | - | - | ||
Gentamicin | 4 | (50) | 6 | (100) | - | - | - | - |
Imipenem | - | - | 6 | (100) | - | - | * | |
Levofloxacin | 5 | (62.5) | 6 | (100) | 3 | (100) | * | |
Meropenem | - | - | 5 | (83.3) | - | - | - | - |
Piperacillin tazobactam | 7 | (87.5) | * | 1 | (33.3) | - | - | |
SXT | * | 5 | (83.3) | 1 | (33.3) | - | - | |
Cefepime | * | 6 | (100) | - | - | * | ||
Tigecycline | * | * | 1 | (33.3) | * |
S. aureus (n = 5) | E. faecium (n = 1) | ||||
---|---|---|---|---|---|
Cefoxitin | 5 | (100) | |||
Clindamycin | - | - | |||
Erythromycin | 1 | (20) | Ampicillin | 1 | (100) |
Linezolid | - | - | HLGR | 1 | (100) |
Rifampin | - | - | Linezolid | - | |
SXT | - | - | Teicoplanin | 1 | (100) |
Tetracycline | - | - | Vancomycin | 1 | (100) |
Univariate Analysis | Multivariate Analysis | ||||
---|---|---|---|---|---|
Variables | Cut-Off | HR (95% Cl) | p | HR (95% Cl) | p |
Age (years) | <65 vs. ≥65 | 1.25 (0.86–1.81) | 0.23 | ||
Gender | Female vs. Male | 1.01 (0.57–1.76) | 0.97 | ||
BMI (kg/m2) | <24.75 vs. ≥24.75 | 1.03 (0.71–1.50) | 0.84 | ||
Pulmonary comorbidity | Yes vs. No | 0.94 (0.62–1.43) | 0.80 | ||
Diabetes mellitus | Yes vs. No | 0.53 (0.34–0.82) | 0.005 | 0.65 (0.40–1.07) | 0.09 |
CCI | <6 vs. ≥6 | 2.25 (1.50–3.36) | <0.001 | 1.40 (0.87–2.25) | 0.16 |
Histopathology | SCC vs. Other | 0.99 (0.68–1.43) | 0.97 | ||
T stage | T1–T2 vs. T3–T4 | 1.23 (0.83–1.82) | 0.29 | ||
N stage | N0 vs. N1–3 | 1.51 (0.92–2.48) | 0.09 | ||
Treatment * | Induction vs. Other | 1.10 (0.72–1.68) | 0.64 | ||
Lymphocyte, 103 | <1.015 vs. ≥1.015 | 0.63 (0.43–0.91) | 0.01 | 0.81 (0.54–1.22) | 0.32 |
Neutrophil, 103 | <3.935 vs. ≥3.935 | 1.32 (0.91–1.91) | 0.14 | ||
Monocyte, 103 | <0.645 vs. ≥0.645 | 0.83 (0.57–1.20) | 0.33 | ||
Platelet, 103 | <239 vs. ≥239 | 1.59 (1.09–2.32) | 0.01 | 1.39 (0.92–2.10) | 0.11 |
CRP (mg/L) | <19.64 vs. ≥19.64 | 1.67 (1.15–2.42) | 0.007 | 1.29 (0.87–1.94) | 0.20 |
Culture | Other vs. Positive | 3.29 (2.20–4.92) | <0.001 | 2.75 (1.78–4.27) | <0.001 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Koca, Ö.; Kahya, U.K.; Beydilli Şahiner, M.; Aksoy, R.A.; Koca, T.; Korcum, A.F. Prognostic Impact of Infectious Agents After Definitive Treatment in Non-Small Cell Lung Cancer. Cancers 2025, 17, 3283. https://doi.org/10.3390/cancers17203283
Koca Ö, Kahya UK, Beydilli Şahiner M, Aksoy RA, Koca T, Korcum AF. Prognostic Impact of Infectious Agents After Definitive Treatment in Non-Small Cell Lung Cancer. Cancers. 2025; 17(20):3283. https://doi.org/10.3390/cancers17203283
Chicago/Turabian StyleKoca, Özlem, Umur Kağan Kahya, Meltem Beydilli Şahiner, Rahmi Atıl Aksoy, Timur Koca, and Aylin Fidan Korcum. 2025. "Prognostic Impact of Infectious Agents After Definitive Treatment in Non-Small Cell Lung Cancer" Cancers 17, no. 20: 3283. https://doi.org/10.3390/cancers17203283
APA StyleKoca, Ö., Kahya, U. K., Beydilli Şahiner, M., Aksoy, R. A., Koca, T., & Korcum, A. F. (2025). Prognostic Impact of Infectious Agents After Definitive Treatment in Non-Small Cell Lung Cancer. Cancers, 17(20), 3283. https://doi.org/10.3390/cancers17203283