{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T20:38:10Z","timestamp":1791664690977,"version":"4.3.4"},"reference-count":29,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Reliable biomarkers that capture tumor\u2013host interactions and predict treatment resistance in extensive-stage small cell lung cancer (SCLC) remain limited. We evaluated the prognostic and predictive value of the pretreatment lactate dehydrogenase-to-albumin ratio (LAR), an integrative biomarker reflecting metabolic activity, systemic inflammation, and host nutritional status. Methods: This multicenter, retrospective cohort study included patients with extensive-stage SCLC treated at five tertiary centers between 2016 and 2024. Pretreatment LAR was calculated using baseline serum lactate dehydrogenase and albumin levels and dichotomized using a Youden index-derived cut-off at the 12-month overall survival (OS) horizon. Time-dependent receiver operating characteristic (ROC) analyses using inverse probability weighting were performed to assess discriminative performance. Survival outcomes were evaluated using Kaplan\u2013Meier estimates and Cox proportional hazards models. Associations with platinum resistance and lack of objective treatment benefit (defined as progressive disease as best response) were examined using logistic regression models. Results: A total of 223 patients were included. Elevated LAR was associated with inferior OS (median, 15.8 vs. 25.2 months; log-rank p &lt; 0.001) and progression-free survival (7.9 vs. 11.5 months; p &lt; 0.001). In multivariable analysis, LAR remained independently associated with OS (HR, 1.43; 95% CI, 1.04\u20131.95; p = 0.028). LAR demonstrated modest but consistently superior discriminative performance compared with other inflammatory indices for both 12-month OS (area under the curve [AUC], 0.692) and 6-month progression-free survival (PFS) (AUC, 0.646), with statistically significant differences in DeLong comparisons. Higher LAR was independently associated with increased odds of platinum resistance (adjusted odds ratio [aOR], 2.31; 95% CI, 1.41\u20133.81; p = 0.001) and lack of objective treatment benefit (adjusted OR, 2.04; 95% CI, 1.33\u20133.14; p = 0.001). Conclusions: Pretreatment LAR is a clinically accessible and biologically integrative biomarker associated with survival and treatment resistance in extensive-stage SCLC. By capturing tumor\u2013host interactions, LAR may support risk stratification and identify patients at increased risk of early treatment failure. Prospective validation is warranted to define its role in biomarker-driven clinical decision-making.<\/jats:p>","DOI":"10.3390\/jcm15093353","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T09:55:39Z","timestamp":1777370139000},"page":"3353","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pretreatment Lactate Dehydrogenase-to-Albumin Ratio and Clinical Outcomes in Extensive-Stage Small Cell Lung Cancer: A Multicenter Real-World Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6654-3815","authenticated-orcid":false,"given":"Ahmet","family":"Unlu","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Antalya Training and Research Hospital, University of Health Sciences, 07100 Antalya, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8749-9825","authenticated-orcid":false,"given":"Asim Armagan","family":"Aydin","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Antalya Training and Research Hospital, University of Health Sciences, 07100 Antalya, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esra Sazimet","family":"Kars","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dicle University Faculty of Medicine, 21100 Diyarbakir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8558-7901","authenticated-orcid":false,"given":"Ozden","family":"Ozturk","sequence":"additional","affiliation":[{"name":"General Directorate of Public Health, Genetic Diseases Screening Laboratory, Ministry of Health, 06100 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet","family":"Acun","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Antalya Training and Research Hospital, University of Health Sciences, 07100 Antalya, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1809-5581","authenticated-orcid":false,"given":"Mehmet Nuri","family":"Baser","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Aydin Adnan Menderes University Faculty of Medicine, 09100 Aydin, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3090-8696","authenticated-orcid":false,"given":"Mahmut","family":"Kara","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dursun Odabas Medical Center, Van Yuzuncu Yil University, 65100 Van, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sati Sena","family":"Coraoglu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Tekirdag Namik Kemal University, 59100 Tekirdag, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurbanu","family":"Inci","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Ataturk Training and Research Hospital, Izmir Katip Celebi University, 35100 Izmir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammet Ali","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dicle University Faculty of Medicine, 21100 Diyarbakir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4380-9419","authenticated-orcid":false,"given":"Bilgin","family":"Demir","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Aydin Adnan Menderes University Faculty of Medicine, 09100 Aydin, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senar","family":"Ebinc","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dursun Odabas Medical Center, Van Yuzuncu Yil University, 65100 Van, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Okan","family":"Avci","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Tekirdag Namik Kemal University, 59100 Tekirdag, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2150-7199","authenticated-orcid":false,"given":"Hacer Boztepe","family":"Yesilcay","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Antalya Training and Research Hospital, University of Health Sciences, 07100 Antalya, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0290-8787","authenticated-orcid":false,"given":"Banu","family":"Ozturk","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Antalya Training and Research Hospital, University of Health Sciences, 07100 Antalya, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa","family":"Yildiz","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Antalya Training and Research Hospital, University of Health Sciences, 07100 Antalya, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41572-020-00235-0","article-title":"Small-Cell Lung Cancer","volume":"7","author":"Rudin","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/S2213-2600(24)00428-4","article-title":"Estimated Worldwide Variation and Trends in Incidence of Lung Cancer by Histological Subtype in 2022 and over Time: A Population-Based Study","volume":"13","author":"Luo","year":"2025","journal-title":"Lancet Respir. Med."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Smolarz, B., \u0141ukasiewicz, H., Samulak, D., Piekarska, E., Ko\u0142aci\u0144ski, R., and Romanowicz, H. (2025). Lung Cancer\u2014Epidemiology, Pathogenesis, Treatment and Molecular Aspect (Review of Literature). Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26052049"},{"key":"ref_4","first-page":"620","article-title":"Clinical Insights into Small Cell Lung Cancer: Tumor Heterogeneity, Diagnosis, Therapy, and Future Directions","volume":"73","author":"Megyesfalvi","year":"2023","journal-title":"CA Cancer J. Clin."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/s41392-022-01013-y","article-title":"Signal Pathways and Precision Therapy of Small-Cell Lung Cancer","volume":"7","author":"Yuan","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1038\/s41571-024-00914-x","article-title":"Emerging Advances in Defining the Molecular and Therapeutic Landscape of Small-Cell Lung Cancer","volume":"21","author":"Sen","year":"2024","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1001\/jama.2025.0560","article-title":"Small Cell Lung Cancer","volume":"333","author":"Kim","year":"2025","journal-title":"JAMA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"107924","DOI":"10.1016\/j.lungcan.2024.107924","article-title":"Five-Year Survival in Patients with Extensive-Stage Small Cell Lung Cancer Treated with Atezolizumab in the Phase III IMpower133 Study and the Phase III IMbrella A Extension Study","volume":"196","author":"Reck","year":"2024","journal-title":"Lung Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1007\/s11864-024-01245-w","article-title":"Small Cell Lung Cancer\u2014An Update on Chemotherapy Resistance","volume":"25","author":"Ying","year":"2024","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1017\/S0007114518002222","article-title":"Nutrition and Cancer: Prevention and Survival","volume":"122","author":"Wiseman","year":"2019","journal-title":"Br. J. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Nishida, A., and Andoh, A. (2025). The Role of Inflammation in Cancer: Mechanisms of Tumor Initiation, Progression, and Metastasis. Cells, 14.","DOI":"10.3390\/cells14070488"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Kuang, Z., Miao, J., and Zhang, X. (2024). Serum Albumin and Derived Neutrophil-to-Lymphocyte Ratio Are Potential Predictive Biomarkers for Immune Checkpoint Inhibitors in Small Cell Lung Cancer. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1327449"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3199","DOI":"10.1007\/s00262-021-02926-3","article-title":"Assessment of Systematic Inflammatory and Nutritional Indexes in Extensive-Stage Small-Cell Lung Cancer Treated with First-Line Chemotherapy and Atezolizumab","volume":"70","author":"Qi","year":"2021","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Wang, B., Zhang, J., Shi, Y., and Wang, Y. (2024). Clinical Significance of the Combined Systemic Immune-Inflammatory Index and Prognostic Nutritional Index in Predicting the Prognosis of Patients with Extensive-Stage Small-Cell Lung Cancer Receiving Immune-Combination Chemotherapy. BMC Cancer, 24.","DOI":"10.1186\/s12885-024-13343-x"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/s41571-022-00686-2","article-title":"The Multiple Roles of LDH in Cancer","volume":"19","author":"Claps","year":"2022","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Daneshmandi, S., Wegiel, B., and Seth, P. (2019). Blockade of Lactate Dehydrogenase-A (LDH-A) Improves Efficacy of Anti-Programmed Cell Death-1 (PD-1) Therapy in Melanoma. Cancers, 11.","DOI":"10.3390\/cancers11040450"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Jiang, M., Wang, Y., Zhao, X., and Yu, J. (2024). From Metabolic Byproduct to Immune Modulator: The Role of Lactate in Tumor Immune Escape. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1492050"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Tang, Q., Li, X., and Sun, C.-R. (2024). Predictive Value of Serum Albumin Levels on Cancer Survival: A Prospective Cohort Study. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1323192"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Chai, D., Yang, T., Zhang, L., Hui, Y., Feng, J., and Wang, W. (2025). Prognostic Value of the Lactate Dehydrogenase to Albumin Ratio in Cancer Patients. Front. Nutr., 12.","DOI":"10.3389\/fnut.2025.1610487"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2956","DOI":"10.21037\/tcr-2024-2577","article-title":"Prognostic Value of Lactate Dehydrogenase to Albumin Ratio in First-Line Chemoimmunotherapy for Locally Advanced or Metastatic Non-Small Cell Lung Cancer","volume":"14","author":"Wei","year":"2025","journal-title":"Transl. Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Zheng, L., Xiong, A., Wang, S., Xu, J., Shen, Y., Zhong, R., Lu, J., Chu, T., Zhang, W., and Li, Y. (2023). Decreased Monocyte-to-Lymphocyte Ratio Was Associated with Satisfied Outcomes of First-Line PD-1 Inhibitors plus Chemotherapy in Stage IIIB-IV Non-Small Cell Lung Cancer. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1094378"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Platini, H., Ferdinand, E., Kohar, K., Prayogo, S., Amirah, S., Komariah, M., and Maulana, S. (2022). Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as Prognostic Markers for Advanced Non-Small-Cell Lung Cancer Treated with Immunotherapy: A Systematic Review and Meta-Analysis. Medicina, 58.","DOI":"10.3390\/medicina58081069"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"104669","DOI":"10.1016\/j.critrevonc.2025.104669","article-title":"Systemic Immune-Inflammation Index as a Predictor of Survival in Non-Small Cell Lung Cancer Patients Undergoing Immune Checkpoint Inhibition: A Systematic Review and Meta-Analysis","volume":"210","author":"Zhang","year":"2025","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1007\/s12094-024-03735-7","article-title":"NRI and SIRI Are the Optimal Combinations for Prognostic Risk Stratification in Patients with Non-Small Cell Lung Cancer after EGFR-TKI Therapy","volume":"27","author":"Liu","year":"2024","journal-title":"Clin. Transl. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1186\/s12957-025-03910-2","article-title":"Pan-Immune-Inflammation Value in Lung Cancer: Prognostic Significance and Implications for Therapeutic Guidance\u2014A Systematic Review and Meta-Analysis","volume":"23","author":"Hong","year":"2025","journal-title":"World J. Surg. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1111\/1759-7714.14484","article-title":"Predictive Value of post-treatment C-reactive Protein-to-albumin Ratio in Locally Advanced non\u2013Small Cell Lung Cancer Patients Receiving Durvalumab after Chemoradiotherapy","volume":"13","author":"Araki","year":"2022","journal-title":"Thorac. Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.2147\/IJGM.S409869","article-title":"Application of Monocyte-to-Albumin Ratio and Neutrophil Percentage-to-Hemoglobin Ratio on Distinguishing Non-Small Cell Lung Cancer Patients from Healthy Subjects","volume":"16","author":"Zhao","year":"2023","journal-title":"Int. J. Gen. Med."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kocianova, E., Piatrikova, V., and Golias, T. (2022). Revisiting the Warburg Effect with Focus on Lactate. Cancers, 14.","DOI":"10.3390\/cancers14246028"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1097\/JN9.0000000000000017","article-title":"Serum Albumin as a Prognostic Predictor Reflecting Host Immunity in Patients with Non\u2013Small Cell Lung Cancer","volume":"8","author":"Li","year":"2023","journal-title":"J. Nutr. Oncol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/9\/3353\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:33:50Z","timestamp":1777372430000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/9\/3353"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,28]]},"references-count":29,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["jcm15093353"],"URL":"https:\/\/doi.org\/10.3390\/jcm15093353","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,28]]}}}